TO ORDER DOCUMENTS: |
Citations from BIOLOGICAL ABSTRACTS: BIO
13. NDN 199-0167-6065-0: Stem cell transplantation for management of primary amyloidosis.
Citations from Federal Research in Progress (FRP): FRP
15. NDN 049-0310-1158-7: Mesenchymal Stem Cells as facilitators of Transplantion Tolerance
16. NDN 049-0310-0958-1: Role of Cell Grafting and Angiogenesis in Infarct Repair
17. NDN 049-0310-0798-5: Stem Cell Therapy and Postinfarction LV Remodeling
18. NDN 049-0310-0174-0: Potential of blood progenitors to form nonblood tissue
19. NDN 049-0309-9400-9: AUGMENTING MYOCARDIAL REGENERATION THROUGH ANGIOGENESIS
20. NDN 049-0309-9300-5: SAFETY AND EFFICACY OF CELLULAR CARDIOMYOPLASTY
21. NDN 049-0309-9112-4: EMBRYONIC ORIGIN OF LYMPHATIC HEART MUSCLE MYOBLASTS
22. NDN 049-0309-8765-0: COLLABORATIVE R01
23. NDN 049-0309-8764-9: CARDIAL GRAFTS--FETAL AND ES DERIVED DONOR CELLS
24. NDN 049-0309-7721-8: DEVELOPING CELLULAR CARDIOMYOPLASTY FOR INJURED HEART
25. NDN 049-0309-4633-7: Adult Stem Cell Therapy For Cardiac Failure
26. NDN 049-0309-4051-7: MYOCARDIAL INFARCT REPAIR
27. NDN 049-0309-4028-1: Gene Transfer And Ex Vivo Manipulation Of Hematopoietic
28. NDN 049-0306-6857-0: LATE EFFECTS IN SURVIVORS OF STEM CELL TRANSPLANTATION
29. NDN 049-0305-3542-8: PATHOGENESIS AND TREATMENT OF CHRONIC REJECTION
Citations from Life Sciences Collection (LSC): LSC
32. NDN 122-0220-9551-1: Proliferation switch for skeletal myoblasts
Citations from MEDLINE(R) DATABASE (2001 TO PRESENT): MED
37. NDN 222-0322-2078-9: Stem cell transplantation for repairment of injured myocardium
39. NDN 222-0321-6946-2: Chimerism of the transplanted heart .
46. NDN 222-0314-2372-3: Mechanical circulatory support--a long and winding road.
48. NDN 222-0309-4009-6: Stem cell research. Stem cells may shore up transplanted hearts.
Citations from PREDICASTS - NEW PRODUCT ANNOUNCEMENTS: NPA
57. NDN 214-0409-3108-9: Cord Blood Registry - Sibling Transplant Success With Umbilical Cord Blood.
Citations from NEWSLETTERS: NWL
59. NDN 102-0261-5414-5: Reprogrammed Human Cells Supply Tissue For Transplantation .
60. NDN 102-0256-5591-6: Autologous Stem Cell Transplantation Can Reduce Damage.
61. NDN 102-0244-4840-0: Transplants Of Siblings' Cells Show Promise For Immune Disorder.
64. NDN 102-0235-1271-3: Doctors transplant skeletal muscle cells into damaged heart .
66. NDN 102-0231-1764-2: Bone Marrow Transplants Show Promise Against Autoimmune Diseases.
67. NDN 102-0228-8350-1: NIH Grant Awarded to Support Cord Blood Transplant Program.
69. NDN 102-0190-6515-1: Blood Banking Umbilical Cord Blood Useful for Transplants .
73. NDN 102-0153-8955-7: Transplantation G-CSF Reduces Ability to Cause Graft-Versus-Host Disease
Citations from PREDICAST F&S INDEX(PFS): PFS
1. Adult
stem
cell
technology: Prospects for cell based therapy in regenerative
medicine.
BIO 05-22
05-294728 NDN-
199-0170-9268-4
Gerlach, J. C.; Zeilinger, K.
JOURNAL NAME- International Journal of
Artificial Organs
VOL. 25
NO. 2
February, 2002
PP.
83-90.
DOCUMENT TYPE- Literature Review
ISSN- 0391-3988
ADDRESS- E-Mail:
joerg.gerlach@charite.de, Forschungshaus Experimentelle Chirurgie Charite -
Campus Virchow Klinikum, Humboldt Universitaet Berlin, Augustenburger Platz
1, 13353, Berlin, Germany
LANGUAGE- ENGLISH
NO-ABSTRACT
DESCRIPTOR(S)- *Cardiovascular System
(Transport and Circulation); *Cell Biology; *Development; *Digestive
System (Ingestion and Assimilation); *Urology (Human Medicine, Medical
Sciences); *human (Hominidae); *Animals; *Chordates; *Humans; *Mammals;
*Primates; *Vertebrates; *adult
stem
cells
--embryonic structure;
*embryonic
stem
cells
--embryonic structure; *
heart
failure --heart
disease; *kidney failure --urologic disease; *liver failure --digestive
system disease; *adult
stem
cell
therapy --therapeutic method;
*immunosuppressive therapy --therapeutic method; *solid organ
transplantation
--surgical method; *solid organ
transplantation
--therapeutic method; *adult
stem
cell
plasticity; *cell based
therapy; *regenerative medicine; *
Heart
Failure, Congestive (MeSH);
*Kidney Failure (MeSH); *Liver Failure (MeSH)
BIOLOGICAL TAXONOMIC DESCRIPTOR(S)- Hominidae --Animalia;
Hominidae --Chordata; Hominidae --Mammalia; Hominidae --Primates;
Hominidae --Vertebrata
BIOSIS Concept Code(s)-
02502; 02506; 02508; 11105; 12512; 14004; 14006; 14504; 14506;
15506; 22018; 25502
BIOSYSTEMATIC CODES-
86215
CHEMICAL INDEXING- print
.
2. Skeletal
myoblast
transplantation
decreases fibrosis and improves regional
function of infarcted myocardial areas.
BIO
05-21 05-275665 NDN- 199-0169-0205-4
Ghostine, Said; Bruneval, Patrick; Carrion, Claire; Hagege,
Albert Alain; Menasche, Philippe; Pouzet, Bruno; Richard, Pascal;
Schwartz, Ketty; Souza, Luiz Cesar Guarita; Vilquin, Jean-Thomas
JOURNAL NAME- Circulation
VOL. 104
NO. 17 Supplement
October 23, 2001
PP. II.600.
DOCUMENT TYPE- Meeting
ISSN-
0009-7322
ADDRESS- Necker Hosp, Paris, France
CONFERENCE DATE- November 11-14, 2001
CONFERENCE TITLE- Scientific Sessions 2001 of the American Heart
Association
LANGUAGE- ENGLISH
NO-ABSTRACT
DESCRIPTOR(S)- *Cardiovascular System
(Transport and Circulation); *Methods and Techniques; *Muscular System
(Movement and Support); *sheep (Bovidae) --animal model; *Animals;
*Artiodactyls; *Chordates; *Mammals; *Nonhuman Mammals; *Nonhuman
Vertebrates; *Vertebrates; *circumflex artery --circulatory system;
*
heart
--circulatory system; *skeletal
myoblasts
--muscular system;
*myocardial infarction --heart disease; *myocardial infarction --pathology;
*myocardial infarction --surgery; *myocardial infarction --therapy;
*myocardial infarction --vascular disease; *collagen; *circumflex artery
embolization --experimental method; *circumflex artery embolization
--surgical method; *computer-based fibrosis quantitation --quantitation
method; *skeletal
myoblasts
transplantation
--surgical method;
*skeletal
myoblasts
transplantation
--tissue
transplantation
method;
*M-mode Doppler tissue imaging --imaging method; *M-mode Doppler tissue
imaging --radiologic method; *diastolic transmural (endocardium-epicardium)
velocity gradient; *ejection fraction; *fibrosis; *global left
ventricular function; *left ventricular end-diastolic volume; *open-chest
injection
; *regional left ventricular function; *segmental wall motion
score; *systolic transmural (endocardium-epicardium) velocity gradient;
*Meeting Abstract; *Myocardial Infarction (MeSH)
BIOLOGICAL TAXONOMIC DESCRIPTOR(S)- Bovidae --Animalia; Bovidae
--Artiodactyla; Bovidae --Chordata; Bovidae --Mammalia; Bovidae
--Vertebrata
BIOSIS Concept Code(s)- 00520; 02506;
10064; 11105; 12502; 12512; 14504; 14506; 14508; 17504
BIOSYSTEMATIC CODES- 85715
CONCEPT
CODE(S)- Anaheim, California, USA
CHEMICAL
INDEXING- print .
3. Long term
functional results of autologous skeletal
myoblast
transplantation
in
rats.
BIO 05-21
05-275662 NDN-
199-0169-0202-9
Pouzet, Bruno; Desnos, Michel; Duboc, Denis; Elattar, Nawwar;
Ghostine, Said; Hagege, Albert A.; Menasche, Philippe; Schwartz, Ketty;
Vilquin, Jean-Thomas
JOURNAL NAME- Circulation
VOL. 104
NO. 17 Supplement
October 23, 2001
PP. II.599.
DOCUMENT TYPE- Meeting
ISSN-
0009-7322
ADDRESS- Hosp Bichat, Paris, France
CONFERENCE DATE- November 11-14, 2001
CONFERENCE TITLE- Scientific Sessions 2001 of the American Heart
Association
LANGUAGE- ENGLISH
NO-ABSTRACT
DESCRIPTOR(S)- *Cardiovascular System
(Transport and Circulation); *Methods and Techniques; *Muscular System
(Movement and Support); *rat (Muridae) --animal model; *Animals;
*Chordates; *Mammals; *Nonhuman Mammals; *Nonhuman Vertebrates;
*Rodents; *Vertebrates; *coronary artery --circulatory system; *skeletal
myoblasts
--muscular system; *tibialis anterior muscle --muscular system;
*myocardial infarction --heart disease; *myocardial infarction --surgery;
*myocardial infarction --therapy; *myocardial infarction --vascular
disease; *autologous skeletal
myoblast
transplantation
--surgical
method; *autologous skeletal
myoblast
transplantation
--therapeutic
method; *autologous skeletal
myoblast
transplantation
--tissue
transplantation
method; *coronary artery ligation --experimental method;
*coronary artery ligation --surgical method; *echocardiography --imaging
method; *echocardiography --measurement method; *echocardiography
--radiologic method; *inferior midline ministernotomy --experimental
method; *inferior midline ministernotomy --surgical method;
*intramyocardial
injection
--administration method; *left thoracotomy
--experimental method; *left thoracotomy --surgical method; *tibialis
anterior muscle biopsy --tissue isolation method; *end-systolic volumes;
*left ventricular remodeling; *long term functional results; *long-term
survivors; *pressure-volume loops; *Meeting Abstract; *Myocardial
Infarction (MeSH)
BIOLOGICAL TAXONOMIC
DESCRIPTOR(S)- Muridae --Animalia; Muridae --Chordata; Muridae
--Mammalia; Muridae --Rodentia; Muridae --Vertebrata
BIOSIS Concept Code(s)- 00520; 02506; 11105; 12512; 14504;
14506; 14508; 17504
BIOSYSTEMATIC CODES-
86375
CONCEPT CODE(S)- Anaheim, California,
USA
CHEMICAL INDEXING- print .
4. Absence of
cardiac differentiation in hematopoietic
stem
cells
transplanted
into
normal and injured hearts.
BIO
05-21 05-275660 NDN- 199-0169-0200-5
Murry, Charles E.; Field, Loren J.; Nakajima, Hidehiro; Nakijima,
Hisako; Rupart, Michael J.; Soonpaa, Mark
JOURNAL NAME- Circulation
VOL. 104
NO. 17 Supplement
October 23, 2001
PP. II.599.
DOCUMENT TYPE- Meeting
ISSN-
0009-7322
ADDRESS- Univ of Washington, Seattle, WA,
USA
CONFERENCE DATE- November 11-14, 2001
CONFERENCE TITLE- Scientific Sessions 2001 of the American
Heart Association
LANGUAGE- ENGLISH
NO-ABSTRACT
DESCRIPTOR(S)- *Cardiovascular System
(Transport and Circulation); *Cell Biology; *mouse (Muridae) --animal
model; *mouse (Muridae) --transgenic; *Animals; *Chordates; *Mammals;
*Nonhuman Mammals; *Nonhuman Vertebrates; *Rodents; *Vertebrates;
*embryonic
stem
cells
--embryonic structure; *
heart
--circulatory
system; *hematopoietic
stem
cells
--blood and lymphatics;
*hematopoietic
stem
cells
--c-kit-positive; *hematopoietic
stem
cells
--cardiac differentiation; *hematopoietic
stem
cells
--Lin-negative; *hematopoietic
stem
cells
--Sca1-positive; *c-kit;
*cardiac alpha-myosin heavy chain promoter; *Lin; *Sca-1; *coronary
occlusion --surgical method; *Meeting Abstract
BIOLOGICAL TAXONOMIC DESCRIPTOR(S)- Muridae --Animalia; Muridae
--Chordata; Muridae --Mammalia; Muridae --Rodentia; Muridae
--Vertebrata
BIOSIS Concept Code(s)- 00520; 02502;
02506; 11105; 12512; 14504; 15002; 15004; 25502
BIOSYSTEMATIC CODES- 86375
CONCEPT
CODE(S)- Anaheim, California, USA
CHEMICAL
INDEXING- print .
5. Early
results of autologous skeletal
myoblast
transplantation
in patients with
severe ischemic
heart
failure.
BIO
05-21 05-275659 NDN- 199-0169-0199-2
Menasche, Philippe; Desnos, Michel; Duboc, Denis; Hagege, Albert
A.; Marolleau, Jean-Pierre; Pouzet, Bruno; Sarateanu, Sorin; Schwartz,
Ketty; Scorsin, Marcio; Vilquin, Jean-Thomas
JOURNAL NAME- Circulation
VOL. 104
NO. 17 Supplement
October 23, 2001
PP. II.598.
DOCUMENT TYPE- Meeting
ISSN-
0009-7322
ADDRESS- Hosp Bichat, Paris, France
CONFERENCE DATE- November 11-14, 2001
CONFERENCE TITLE- Scientific Sessions 2001 of the American Heart
Association
LANGUAGE- ENGLISH
NO-ABSTRACT
DESCRIPTOR(S)- *Cardiovascular Medicine
(Human Medicine, Medical Sciences); *Muscular System (Movement and
Support); *Surgery (Medical Sciences); *human (Hominidae) --patient;
*Animals; *Chordates; *Humans; *Mammals; *Primates; *Vertebrates;
*
heart
--circulatory system; *skeletal
myoblasts
; *hypotension
--vascular disease; *severe ischemic
heart
failure --heart disease;
*severe ischemic
heart
failure --surgery; *severe ischemic
heart
failure --therapy; *severe ischemic
heart
failure --vascular disease;
*gadolinium --diagnostic-drug; *gadolinium --uptake; *autologous skeletal
myoblast
transplantation
--complications; *autologous skeletal
myoblast
transplantation
--efficacy; *autologous skeletal
myoblast
transplantation
--safety; *autologous skeletal
myoblast
transplantation
--surgical method; *autologous skeletal
myoblast
transplantation
--therapeutic method; *autologous skeletal
myoblast
transplantation
--tissue
transplantation
method; *coronary anastomosis
--surgical method; *dobutamine stress echocardiography --imaging method;
*dobutamine stress echocardiography --radiologic method;
*fluorodeoxyglucose positron emission tomography --imaging method;
*fluorodeoxyglucose positron emission tomography --radiologic method;
*magnetic resonance imaging --imaging method; *magnetic resonance imaging
--radiologic method; *magnetic resonance imaging --Imaging Techniques;
*discrete post-infarction scar; *left ventricular function; *Meeting
Abstract; *Hypotension (MeSH)
BIOLOGICAL TAXONOMIC
DESCRIPTOR(S)- Hominidae --Animalia; Hominidae --Chordata; Hominidae
--Mammalia; Hominidae --Primates; Hominidae --Vertebrata
BIOSIS Concept Code(s)- 00520; 02506; 02508; 10069; 11105;
12504; 12512; 14504; 14506; 14508; 17504
BIOSYSTEMATIC CODES- 86215
CAS REGISTRY/EC
NUMBER(S)- *7440-54-2 --GADOLINIUM
CONCEPT
CODE(S)- Anaheim, California, USA
CHEMICAL
INDEXING- print .
6. Genetically
engineered
myoblasts
survive allogeneic
transplant
into
myocardium
.
BIO 05-21
05-275237 NDN-
199-0168-9777-0
Aston, Ashley G.; Colgrove, Sharon L.; Ellis, Matthew J.; Emani,
Sitaram M.; Pineles, Stacy L.; Taylor, Doris A.
JOURNAL NAME- Circulation
VOL. 104
NO. 17 Supplement
October 23, 2001
PP. II.324.
DOCUMENT TYPE- Meeting
ISSN-
0009-7322
ADDRESS- Duke Univ, Durham, NC, USA
CONFERENCE DATE- November 11-14, 2001
CONFERENCE TITLE- Scientific Sessions 2001 of the American Heart
Association
LANGUAGE- ENGLISH
NO-ABSTRACT
DESCRIPTOR(S)- *Cardiovascular System
(Transport and Circulation); *animal (Animalia); *Animals; *
myoblast
--muscular system; *
myocardium
--circulatory system; *
myocardium
--muscular system; *cleavable Fas ligand; *uncleavable Fas ligand
--expression; *allogenic
transplantation
--therapeutic method; *Meeting
Abstract
BIOLOGICAL TAXONOMIC DESCRIPTOR(S)-
Animalia
BIOSIS Concept Code(s)- 00520; 02506;
12512; 14504; 17504
BIOSYSTEMATIC CODES-
33000
CONCEPT CODE(S)- Anaheim, California,
USA
CHEMICAL INDEXING- print .
7. Effects of
co-transplantation of cultured human mesenchymal
stem
cells
plus fetal
cardiomyocytes on cardiac function in infarcted pigs.
BIO 05-21
05-275066 NDN-
199-0168-9606-6
Zhang, Jian-Ping; Yang, Yinke; Xiao, Yong-Fu; Sullivan, Matthew
F.; Morgan, James P.; Min, Jiang-Yong; Converso, Kimber L.
JOURNAL NAME- Circulation
VOL. 104
NO. 17 Supplement
October 23, 2001
PP. II.289.
DOCUMENT TYPE- Meeting
ISSN-
0009-7322
ADDRESS- Beth Israel Deaconess Med Ctr,
Boston, MA, USA
CONFERENCE DATE- November 11-14,
2001
CONFERENCE TITLE- Scientific Sessions 2001 of
the American Heart Association
LANGUAGE-
ENGLISH
NO-ABSTRACT
DESCRIPTOR(S)- *Cardiovascular System
(Transport and Circulation); *Methods and Techniques; *human (Hominidae);
*Yorkshire pig (Suidae) --fetus; *Yorkshire pig (Suidae) --male; *Animals;
*Artiodactyls; *Chordates; *Humans; *Mammals; *Nonhuman Mammals;
*Nonhuman Vertebrates; *Primates; *Vertebrates; *cardiomyocyte
--circulatory system; *cardiomyocyte --muscular system; *mesenchymal
stem
cell
--embryonic structure; *myocardial infarction --heart
disease; *myocardial infarction --vascular disease; *myosin heavy chain
--expression; *troponin I --expression; *GFP green fluorescent protein ;
*cardiomyocyte
transplantation
--therapeutic method; *mesenchymal
stem
cell
transplantation
--therapeutic method; *blood flow; *cardiac
function; *ventricular function; *Meeting Abstract; *Myocardial
Infarction (MeSH)
BIOLOGICAL TAXONOMIC
DESCRIPTOR(S)- Hominidae --Animalia; Hominidae --Chordata; Hominidae
--Mammalia; Hominidae --Primates; Hominidae --Vertebrata; Suidae
--Animalia; Suidae --Artiodactyla; Suidae --Chordata; Suidae --Mammalia;
Suidae --Vertebrata
BIOSIS Concept Code(s)- 00520;
02506; 02508; 10064; 12512; 14504; 14506; 14508; 17504; 25502
BIOSYSTEMATIC CODES- 85740; 86215
CONCEPT CODE(S)- Anaheim, California, USA
CHEMICAL INDEXING- print .
8. Embryonic
stem
cell
transplantation
for repair of infarcted
myocardium
and
functional improvement with long-term follow up.
BIO 05-21
05-275064 NDN-
199-0168-9604-2
Yang, Yinke; Xiao, Yong-Fu; Sullivan, Matthew F.; Morgan, James
P.; Min, Jiang-Yong; Ke, Qingen; Converso, Kimber L.
JOURNAL NAME- Circulation
VOL. 104
NO. 17 Supplement
October 23, 2001
PP. II.288-II.289.
DOCUMENT TYPE- Meeting
ISSN-
0009-7322
ADDRESS- Beth Israel Deaconess Med Ctr,
Boston, MA, USA
CONFERENCE DATE- November 11-14,
2001
CONFERENCE TITLE- Scientific Sessions 2001 of
the American Heart Association
LANGUAGE-
ENGLISH
NO-ABSTRACT
DESCRIPTOR(S)- *Cardiovascular System
(Transport and Circulation); *Methods and Techniques; *Wistar rat
(Muridae) --male; *Animals; *Chordates; *Mammals; *Nonhuman Mammals;
*Nonhuman Vertebrates; *Rodents; *Vertebrates; *embryonic
stem
cell
--embryonic structure; *left descending coronary artery --circulatory
system; *
myocardium
--circulatory system; *
myocardium
--muscular
system; *myocardial infarction --heart disease; *myocardial infarction
--therapy; *myocardial infarction --vascular disease; *green fluorescent
protein; *myosin heavy chain; *troponin I; *embryonic
stem
cell
transplantation
--efficacy; *embryonic
stem
cell
transplantation
--therapeutic method; *cardiac function; *left ventricular end-diastolic
pressure; *left ventricular systolic pressure; *survival rate;
*ventricular function; *Meeting Abstract; *Myocardial Infarction
(MeSH)
BIOLOGICAL TAXONOMIC DESCRIPTOR(S)- Muridae
--Animalia; Muridae --Chordata; Muridae --Mammalia; Muridae --Rodentia;
Muridae --Vertebrata
BIOSIS Concept Code(s)- 00520;
02506; 10064; 12512; 14504; 14506; 14508; 17504; 25502
BIOSYSTEMATIC CODES- 86375
CONCEPT
CODE(S)- Anaheim, California, USA
CHEMICAL
INDEXING- print .
9. Cardiogenesis and angiogenesis in infarcted
myocardium
by
intramyocardial
transplantation
of embryonic
stem
cells
in mice.
BIO 05-21
05-274976 NDN-
199-0168-9516-5
Yang, Yinke; Xiao, Yong-Fu; Morgan, James P. P.; Min, Jiang-Yong;
Ke, Qingen; Cai, Jingbo
JOURNAL NAME- Circulation
VOL. 104
NO. 17 Supplement
October 23, 2001
PP. II.270.
DOCUMENT TYPE- Meeting
ISSN-
0009-7322
ADDRESS- Beth Israel Deaconess Med Ctr,
Harvard Med Sch, Boston, MA, USA
CONFERENCE DATE-
November 11-14, 2001
CONFERENCE TITLE- Scientific
Sessions 2001 of the American Heart Association
LANGUAGE- ENGLISH
NO-ABSTRACT
DESCRIPTOR(S)- *Cardiovascular System
(Transport and Circulation); *Methods and Techniques; *mouse (Muridae);
*Animals; *Chordates; *Mammals; *Nonhuman Mammals; *Nonhuman
Vertebrates; *Rodents; *Vertebrates; *blood vessel --circulatory system;
*embryonic
stem
cell
--blood and lymphatics; *
heart
--circulatory
system; *left anterior descending coronary artery --circulatory system;
*left ventricle --circulatory system; *
myocardium
--circulatory system;
*
myocardium
--muscular system; *myocardial infarction --heart disease;
*myocardial infarction --vascular disease; *vascular endothelial growth
factor; *embryonic
stem
cell
intramyocardial
transplantation
--intervention method; *left anterior descending coronary artery ligation
--intervention method; *angiogenesis; *cardiogenesis; *left ventricular
systolic pressure --regulation; *Meeting Abstract; *Myocardial Infarction
(MeSH)
BIOLOGICAL TAXONOMIC DESCRIPTOR(S)- Muridae
--Animalia; Muridae --Chordata; Muridae --Mammalia; Muridae --Rodentia;
Muridae --Vertebrata
BIOSIS Concept Code(s)- 00520;
02506; 10064; 14504; 14506; 14508; 15002; 15004; 17002; 17504
BIOSYSTEMATIC CODES- 86375
CAS
REGISTRY/EC NUMBER(S)- *127464-60-2 --VASCULAR ENDOTHELIAL GROWTH
FACTOR
CONCEPT CODE(S)- Anaheim, California,
USA
CHEMICAL INDEXING- print .
10. Total body
irradiation (TBI) with
stem
cell
transplantation
(SCT) in multiple
myeloma (MM).
BIO 05-20
05-264838 NDN-
199-0167-9378-2
Perry, G.; Genest, P.; Donker, R.; Dahrouge, S.; Atkins, H.;
Bence-Bruckler, I.; Bredeson, C.; Huebsch, L.
JOURNAL NAME- European Journal of
Cancer
VOL. 37
NO.
Supplement 6
October, 2001
PP.
S98.
DOCUMENT TYPE- Meeting
ISSN- 0959-8049
ADDRESS- Radiation
Oncology, Ottawa Regional Cancer Centre, Ottawa, ON, Canada
CONFERENCE DATE- October 21-25, 2001
CONFERENCE TITLE- 11th European Cancer Conference
LANGUAGE- ENGLISH
NO-ABSTRACT
DESCRIPTOR(S)- *Clinical Immunology
(Human Medicine, Medical Sciences); *Hematology (Human Medicine, Medical
Sciences); *Oncology (Human Medicine, Medical Sciences); *human
(Hominidae) --patient; *Animals; *Chordates; *Humans; *Mammals;
*Primates; *Vertebrates; *arrhythmia --heart disease; *arrhythmia
--injury; *arrhythmia --toxicity; *dysphagia --dental and oral disease;
*dysphagia --toxicity; *hypogonadism --endocrine disease/gonads;
*hypogonadism --injury; *hypogonadism --toxicity; *hypothyroidism
--endocrine disease/thyroid; *hypothyroidism --injury; *hypothyroidism
--toxicity; *mucositis --dental and oral disease; *mucositis --digestive
system disease; *mucositis --immune system disease; *mucositis
--toxicity; *multiple myeloma --blood and lymphatic disease; *multiple
myeloma --immune system disease; *multiple myeloma --neoplastic disease;
*multiple myeloma --radiotherapy; *
stem
cell
transplantation
--therapeutic method; *
stem
cell
transplantation
--tissue
transplantation
method; *total body irradiation --conditioning regimen;
*total body irradiation --radiologic method; *total body irradiation
--therapeutic method; *Meeting Abstract; *Meeting Poster; *Arrhythmia
(MeSH); *Deglutition Disorders (MeSH); *Hypogonadism (MeSH);
*Hypothyroidism (MeSH); *Multiple Myeloma (MeSH)
BIOLOGICAL TAXONOMIC DESCRIPTOR(S)- Hominidae --Animalia;
Hominidae --Chordata; Hominidae --Mammalia; Hominidae --Primates;
Hominidae --Vertebrata
BIOSIS Concept Code(s)-
00520; 12512; 14006; 14506; 15006; 17006; 17018; 19006; 22501;
24004; 24008; 24010; 34508
BIOSYSTEMATIC CODES-
86215
CONCEPT CODE(S)- Lisbon, Portugal
CHEMICAL INDEXING- print .
11. The fate of
skeletal
myoblasts
following
transplantation
into infarcted rat
myocardium
.
BIO 05-20
05-264465 NDN-
199-0167-9005-7
Garcin, Isabelle; Carrion, Claire; Duboc, Denis; Fiszman, Marc
Y.; Hagege, Albert A.; Menasche, Philippe; Pouzet, Bruno; Schwartz,
Ketty; Vilquin, Jean-Thomas
JOURNAL NAME- Circulation
VOL. 104
NO. 17 Supplement
October 23, 2001
PP. II.555.
DOCUMENT TYPE- Meeting
ISSN-
0009-7322
ADDRESS- INSERM U523, Groupe Hospitalier
Pitie-Salpetriere, Paris, France
CONFERENCE DATE-
November 11-14, 2001
CONFERENCE TITLE- Scientific
Sessions 2001 of the American Heart Association
LANGUAGE- ENGLISH
NO-ABSTRACT
DESCRIPTOR(S)- *Cardiovascular System
(Transport and Circulation); *Molecular Genetics (Biochemistry and
Molecular Biophysics); *Muscular System (Movement and Support); *rat
(Muridae); *Animals; *Chordates; *Mammals; *Nonhuman Mammals;
*Nonhuman Vertebrates; *Rodents; *Vertebrates; *capillary --circulatory
system; *coronary vessel --circulatory system; *endothelium --circulatory
system; *
heart
--circulatory system; *
myocardium
--circulatory
system; *
myocardium
--muscular system; *skeletal
myoblast
--fast;
*skeletal
myoblast
--muscular system; *skeletal
myoblast
--skeletal
system; *skeletal
myoblast
--slow; *myocardial infarction --heart
disease; *myocardial infarction --vascular disease; *slow myosin heavy
chain; *
transplantation
--tissue
transplantation
method;
*angiogenesis; *cardiac-type workload; *Meeting Abstract; *Myocardial
Infarction (MeSH)
BIOLOGICAL TAXONOMIC
DESCRIPTOR(S)- Muridae --Animalia; Muridae --Chordata; Muridae
--Mammalia; Muridae --Rodentia; Muridae --Vertebrata
BIOSIS Concept Code(s)- 00520; 02506; 03502; 03506; 14504;
14506; 14508; 17504; 18004
BIOSYSTEMATIC CODES-
86375
CONCEPT CODE(S)- Anaheim, California,
USA
CHEMICAL INDEXING- print .
12. High dose
intravenous melphalan and autologous
stem
cell
transplantation
for
the treatment of AL amyloidosis: Morbidity and mortality.
BIO 05-20
05-261704 NDN-
199-0167-6244-0
Wright, Daniel G.; Taper, John; Skinner, Martha; Seldin, David
C.; Sanchorawala, Vaishali; Quillen, Karen; Finn, Kathleen; Falk,
Rodney H.; Dember, Laura; Berk, John
JOURNAL NAME- Blood
VOL. 98
NO. 11 Part 1
November 16, 2001
PP. 860a.
DOCUMENT TYPE- Meeting
ISSN-
0006-4971
ADDRESS- Boston University Medical
Center, Boston, MA, USA
CONFERENCE DATE- December
07-11, 2001
CONFERENCE TITLE- 43rd Annual Meeting
of the American Society of Hematology, Part 1
LANGUAGE- ENGLISH
AL amyloidosis is caused by a clonal plasma cell dyscrasia and
characterized by widespread, progressive amyloid deposition leading to
multisystem organ failure and death. Aggressive treatment of AL amyloidosis
with high dose intravenous melphalan followed by autologous stem cell
transplant (HDM/SCT) is effective in inducing hematologic and clinical
remissions and in extending survival. However, in our experience HDM/SCT is
a challenging and toxic treatment for AL amyloidosis patients, given their
multisystem disease. Morbidity and mortality is associated with all phases
of HDM/SCT: during stem cell mobilization and collection, during
post-treatment myelosuppression, and following hematopoietic engraftment.
Between 6/94 and 3/01, 250 patients with AL amyloidosis, (median age=57,
range 29-80), began HDM/SCT treatment protocols at Boston University
Medical Center. A majority had clinically evident renal involvement, and
53% had echocardiographic evidence of cardiac involvement. Overall
mortality during the 3-month peri-transplant period was 14%. Of the 250
patients who began the stem cell mobilization and collection phase of
treatment, 27 (11%) did not proceed to HDM/SCT, either because of death
(4%) or major toxicities (7%). Deaths were associated with sudden cardiac
arrest or irreversible congestive heart failure in 5 patients during stem
cell mobilization with high dose G-SCF, or during or soon after apheresis
for stem cell collection in 3 cases. Other causes of death included
mesenteric vein thrombosis with sepsis and massive GI bleeding. Major
morbidity occurred in 23 patients during stem cell mobilization and
collection; of these 18 did not proceeded to HDM/SCT. Morbid events
included hypotension and/or arrhythmias during apheresis, catheter-related
thromboses, GI bleeding, femoral artery embolus, and Klebsiella bacteremia.
Sixteen deaths occurred during the stem cell transplant phase of treatment,
primarily from cardiac events. There were 4 cardiac arrests leading to
death during stem cell infusion, and 6 during the following 4 weeks. Other
lethal events were GI perforation or hemorrhage and sepsis. During stem
cell infusions, significant bradycardia and/or hypotension occurred in 8
patients, and 1 patient subsequently suffered an embolic CVA. As expected,
the principal morbidity during the immediate post-transplant period was
febrile neutropenia, which occurred in apprx25% of patients. GI hemorrhage
requiring transfusion support occurred in 17 patients, while progression of
renal dysfunction to renal failure necessitation dialysis occurred in 12.
Following hematopoietic engraftment and recovery, 2 patients with severe
Factor X deficiency suffered spontaneous splenic rupture necessitating
splenectomy, and 4 patients died from pneumonitis/respiratory failure
syndromes. In summary, HDM/SCT in AL amyloidosis presents unique clinical
challenges, particularly because of the cardiovascular instability of
patients and the risks of both thrombosis and bleeding. Both clinicians and
patients who proceed with this aggressive form of therapy must be prepared
for both the usual and unusual toxicities that may occur.
DESCRIPTOR(S)- *Cardiovascular
Medicine (Human Medicine, Medical Sciences); *Clinical Immunology (Human
Medicine, Medical Sciences); *Hematology (Human Medicine, Medical
Sciences); *Pharmacology; *human (Hominidae) --adult; *human (Hominidae)
--aged; *human (Hominidae) --aged/80 and over; *human (Hominidae) --host;
*human (Hominidae) --middle age; *human (Hominidae) --patient;
*Klebsiella (Enterobacteriaceae) --pathogen; *Animals; *Bacteria;
*Chordates; *Eubacteria; *Humans; *Mammals; *Microorganisms;
*Primates; *Vertebrates; *femoral artery --circulatory system; *
heart
--circulatory system; *kidney --excretory system; *mesenteric vein
--circulatory system; *mesenteric vein --digestive system; *spleen
--blood and lymphatics; *spleen --immune system; *GI gastrointestine
--digestive system; *bradycardia --heart disease; *cardiac arrest --heart
disease; *congestive
heart
failure --heart disease; *febrile
neutropenia --blood and lymphatic disease; *febrile neutropenia
--toxicity; *femoral artery embolism --blood and lymphatic disease;
*femoral artery embolism --vascular disease; *hypotension --vascular
disease; *mesenteric vein thrombosis --blood and lymphatic disease;
*mesenteric vein thrombosis --digestive system disease; *mesenteric vein
thrombosis --vascular disease; *renal failure --urologic disease;
*respiratory failure --respiratory system disease; *splenic rupture
--blood and lymphatic disease; *splenic rupture --injury; *sudden cardiac
death --heart disease; *AL amyloidosis --blood and lymphatic disease; *AL
amyloidosis --immune system disease; *AL amyloidosis --metabolic disease;
*AL amyloidosis --mortality; *AL amyloidosis --therapy; *Factor X
deficiency --blood and lymphatic disease; *Factor X deficiency --genetic
disease; *GI bleeding gastrointestinal bleeding --digestive system
disease; *GI bleeding gastrointestinal bleeding --vascular disease;
*Klebsiella bacteremia --bacterial disease; *Klebsiella bacteremia
--infectious disease; *high dose melphalan --hematologic-drug; *high dose
melphalan --immunologic-drug; *high dose melphalan --toxicity; *high dose
G-SCF high dose granulocyte colony stimulating factor --hematologic-drug;
*Factor X; *apheresis --collection method; *autologous
stem
cell
transplantation
--complications; *autologous
stem
cell
transplantation
--efficacy; *autologous
stem
cell
transplantation
--therapeutic method; *
stem
cell
mobilization --intervention method;
*transfusion support --therapeutic method; *drug efficacy; *Meeting
Abstract; *Bradycardia (MeSH); *Death, Sudden, Cardiac (MeSH); *
Heart
Arrest (MeSH); *
Heart
Failure, Congestive (MeSH); *Hypotension (MeSH);
*Kidney Failure (MeSH); *Respiratory Insufficiency (MeSH); *Splenic
Rupture (MeSH)
BIOLOGICAL TAXONOMIC DESCRIPTOR(S)-
Enterobacteriaceae --Bacteria; Enterobacteriaceae --Eubacteria;
Enterobacteriaceae --Facultatively Anaerobic Gram-Negative Rods;
Enterobacteriaceae --Microorganisms; Hominidae --Animalia; Hominidae
--Chordata; Hominidae --Mammalia; Hominidae --Primates; Hominidae
--Vertebrata
BIOSIS Concept Code(s)- 00520; 03508;
12512; 13020; 14004; 14006; 14504; 14506; 14508; 15002; 15004;
15006; 15504; 15506; 16006; 22002; 22005; 22008; 22018; 22501;
22504; 24500; 31000; 34502; 34508; 36001; 36002
BIOSYSTEMATIC CODES- 06702; 86215
CAS
REGISTRY/EC NUMBER(S)- *9001-29-0 --FACTOR X
CONCEPT CODE(S)- Orlando, Florida, USA
CHEMICAL INDEXING- print .
13.
Stem
cell
transplantation
for management of primary amyloidosis.
BIO 05-20
05-261525 NDN-
199-0167-6065-0
Tefferi, A.; Micallef, I. N.; Litzow, M. R.; Lacy, M. Q.;
Inwards, D. J.; Gertz, Morie A.; Gastineau, D. A.; Dispenzieri, A.;
Ansell, S. M.; Chen, M. G.
JOURNAL NAME- Blood
VOL. 98
NO. 11 Part 1
November 16, 2001
PP. 816a.
DOCUMENT TYPE- Meeting
ISSN-
0006-4971
ADDRESS- Division of Hematology, Mayo
Clinic, Rochester, MN, USA
CONFERENCE DATE-
December 07-11, 2001
CONFERENCE TITLE- 43rd Annual
Meeting of the American Society of Hematology, Part 1
LANGUAGE- ENGLISH
INTRODUCTION: Amyloidosis (AL) results from the deposition of
immunoglobulin light chain fragments. The median survival of patients is
one year. Stem cell transplantation provides higher response rates than
achievable with onventional chemotherapy. This abstract reviews the Mayo
Clinic experience with stem cell transplant for AL. MATERIALS AND METHODS:
All patients had biopsy-proven AL with an immunoglobulin light chain in
blood, urine or clonal bone marrow plasma cells. Patients with overt
multiple myeloma were excluded. RESULTS: The histologic diagnosis of AL was
established by biopsy of rectum, kidney, liver, heart, marrow and fat in 9,
29, 6, 16, 49 and 46 patients, respectively. By echocardiography 35
patients had a septal thickness of less than 12 mm, 23 a septal thickness
ranging from 13 to 15 mm and 8 had a septal thickness greater than or equal
to 16 mm. Nine patients had an ejection fraction less than 60%. The median
time from histologic diagnosis of amyloid to transplant was 5 months. Ten
of the patients were transplanted one year or greater after diagnosis.
Thirty-three patients were mobilized using Cyclophosphamide plus GM-CSF.
Thirty-three patients received G-CSF with stem cell collection on day 5.
The median number of aphereses required to achieve a stem cell count of
2X106 cells/kg was 3 in the Cyclophosphamide group and 2 in the G-CSF group
(p<0.01). Nine patients required dialysis post-transplant. Seven
patients died. The median serum creatinine of patients requiring dialysis
was 1.7 mg/dL compared with 1.1 mg/dL for the 57 patients who did not
dialyze (p<0.01). None of the patients with an ejection fraction less
than 60% died in the first 100 days. None of the 8 patients transplanted
with a ventricular septal thickness of greater than or equal to 16 died
within the first 100 days. Nine of the patients died prior to day 100, a
treatment-related mortality of 14%. There was a high incidence of
gastrointestinal bleeding following conditioning. The actuarial survival at
24 months is 75%. The number of organs involved was the single most
important feature predictive of outcome. The median time to response was
3.6 months, but 6 renal patients took greater than 1 year and 1 patient
took 28 months. DISCUSSION: Stem cell transplant has been demonstrated to
produce a high response rate in AL. The best responses are seen in isolated
renal amyloidosis. The number of aphereses required is lower in patients
mobilized with G-CSF alone than it is with Cyclophosphamide plus GM-CSF. An
elevated serum creatinine raises the risk of requiring dialysis during
transplantation. Patients over the age of 60 or with a serum creatinine
greater than 2.0 can be transplanted with a reduced Melphalan dose. The
number of organs involved pretransplant is the key predictor of
outcome.
DESCRIPTOR(S)- *Clinical Immunology
(Human Medicine, Medical Sciences); *Hematology (Human Medicine, Medical
Sciences); *Metabolism; *human (Hominidae) --patient; *Animals;
*Chordates; *Humans; *Mammals; *Primates; *Vertebrates; *blood --blood
and lymphatics; *bone marrow plasma cell --blood and lymphatics; *bone
marrow plasma cell --immune system; *fat; *
heart
--circulatory system;
*kidney --excretory system; *liver --digestive system; *rectum
--digestive system; *serum --blood and lymphatics; *urine --excretory
system; *gastrointestinal bleeding --digestive system disease;
*gastrointestinal bleeding --toxicity; *primary amyloidosis --blood and
lymphatic disease; *primary amyloidosis --immune system disease; *primary
amyloidosis --metabolic disease; *primary amyloidosis --mortality;
*primary amyloidosis --therapy; *renal amyloidosis --blood and lymphatic
disease; *renal amyloidosis --immune system disease; *renal amyloidosis
--metabolic disease; *renal amyloidosis --therapy; *renal amyloidosis
--urologic disease; *creatinine; *cyclophosphamide --hematologic-drug;
*G-CSF granulocyte-colony stimulating factor --hematologic-drug; *GM-CSF
granulocyte-macrophage colony stimulating factor --hematologic-drug;
*dialysis --crystallization; *dialysis --therapeutic method; *
stem
cell
transplantation
--therapeutic method; *ventricular septal
thickness; *Meeting Abstract; *Gastrointestinal Hemorrhage (MeSH)
BIOLOGICAL TAXONOMIC DESCRIPTOR(S)- Hominidae --Animalia;
Hominidae --Chordata; Hominidae --Mammalia; Hominidae --Primates;
Hominidae --Vertebrata
BIOSIS Concept Code(s)-
00520; 10060; 10064; 10066; 12512; 13002; 13020; 14004; 14006;
14504; 15002; 15004; 15006; 15504; 15506; 17002; 22005; 22008;
22501; 22504; 34502; 34508
BIOSYSTEMATIC CODES-
86215
CAS REGISTRY/EC NUMBER(S)- *143011-72-7
--GRANULOCYTE-COLONY STIMULATING FACTOR; *50-18-0 --CYCLOPHOSPHAMIDE;
*60-27-5 --CREATININE; *83869-56-1 --GM-CSF; *83869-56-1
--GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR
CONCEPT CODE(S)- Orlando, Florida, USA
CHEMICAL INDEXING- print .
14. Circulating
human fetal stromal cells engraft and differentiate in multiple tissues
following
transplantation
into preimmune lamb fetuses.
BIO 05-20
05-261453 NDN-
199-0167-5993-2
Radu, Antoneta; MacKenzie, Tippi C.; Flake, Alan W.;
Almeida-Porada, Graca; Campagnoli, Cesare; Fisk, Nicholas
JOURNAL NAME- Blood
VOL. 98
NO. 11 Part 1
November 16, 2001
PP. 798a.
DOCUMENT TYPE- Meeting
ISSN-
0006-4971
ADDRESS- Children's Institute for
Surgical Science, Children's Hospital of Philadelphia, Philadelphia, PA,
USA
CONFERENCE DATE- December 07-11, 2001
CONFERENCE TITLE- 43rd Annual Meeting of the American
Society of Hematology, Part 1
LANGUAGE-
ENGLISH
Characterization of circulating fetal cells with the capacity to
seed, differentiate, and persist in multiple tissue compartments may
provide insights into the process of normal tissue development, repair, and
regeneration. We (C.C. and N.F.) have previously characterized a population
of circulating human fetal stromal cells with multipotential
differentiative capacity in vitro, similar to adult bone marrow (BM)
derived mesenchymal stem cells (MSC). Since we have previously shown that
adult human MSC can engraft and show multilineage differentiation in a
fetal lamb model, we used this model to test the in vivo differentiative
capacity of fetal MSC. Fetal MSC were isolated by culturing the nucleated,
plastic-adherent fraction of blood obtained from human fetuses at 9-11
weeks gestation. After expansion for 1-2 passages, these cells were
transplanted into fetal lambs at 55-60 days gestation (term=145 days)
intraperitoneally at a dose of 1e8 cells/kg. The lambs were sacrificed at 2
months (n=6), 4 months (n=4), and 6 months (n=4) and tissues were analyzed
for the presence of human cells using PCR for human HLA-DR, staining for
human beta-2 microglobulin, and in situ hybridization (ISH) for human Alu
sequences. At two months, PCR analysis showed engraftment in liver (3/6),
spleen (4/6), thymus (3/6), heart (3/6), lung (2/6), muscle (3/6),
cartilage (3/6), tendon (2/6), aorta (3/6), brain (5/6), skin (1/6), blood
(2/6), and bone marrow (2/6). At 4 months, only brain (2/4) and blood (2/4)
were positive whereas at 6 months, only liver (1/4), heart (1/4) and
omentum (1/4) had evidence of engraftment by PCR. Human cells were detected
by in situ hybridization in liver, bone marrow, cartilage, brain, and aorta
and by immunohistochemistry for human beta-2 microglobulin in spleen. Cells
in the liver were located in periportal, perivascular, and parenchymal
areas. Nuclei were detected in the lacunae of cartilage, indicating
potential chondrocytic differentiation. FACS of peripheral blood for CD45
was positive at 2.8% and 0.8% for two animals which also had PCR evidence
of human cells in the blood. CD45 and CD23 staining of bone marrow was also
positive, indicating potential hematopoietic and stromal cell
differentiation. We conclude from this data that circulating human fetal
stromal cells engraft in multiple tissues and may differentiate into
chondrocytes, stromal cells, and hematopoietic elements, as well as other
unidentified cell types, following in utero transplantation. These results
support the concept that early gestational circulating cells may contribute
to the generation of a BM microenvironment and hematopoiesis. The seeding
of multiple tissue compartments during gestation may allow these cells to
participate in organ formation and to form a reservoir for adult tissue
repair and regeneration.
DESCRIPTOR(S)- *Blood and Lymphatics
(Transport and Circulation); *Development; *sheep (Bovidae) --fetus;
*sheep (Bovidae) --lamb; *Animals; *Artiodactyls; *Chordates; *Mammals;
*Nonhuman Mammals; *Nonhuman Vertebrates; *Vertebrates; *aorta
--circulatory system; *blood --blood and lymphatics; *bone marrow --blood
and lymphatics; *bone marrow --immune system; *brain --nervous system;
*cartilage --skeletal system; *
heart
--circulatory system;
*hematopoietic cell --blood and lymphatics; *liver --digestive system;
*lung --respiratory system; *mesenchymal
stem
cell
--differentiation;
*muscle --muscular system; *omentum; *skin --integumentary system;
*spleen --blood and lymphatics; *spleen --immune system; *tendon
--skeletal system; *thymus --blood and lymphatics; *thymus --endocrine
system; *thymus --immune system; *beta-2 microglobulin; *Alu; *CD23
--expression; *CD45 --expression; *HLA-DR; *cell engraftment; *Meeting
Abstract
BIOLOGICAL TAXONOMIC DESCRIPTOR(S)-
Bovidae --Animalia; Bovidae --Artiodactyla; Bovidae --Chordata; Bovidae
--Mammalia; Bovidae --Vertebrata
BIOSIS Concept
Code(s)- 00520; 02506; 10064; 14004; 14504; 15002; 15004; 16004;
17002; 17020; 17504; 18004; 18504; 20504; 25502; 34502
BIOSYSTEMATIC CODES- 85715
CONCEPT
CODE(S)- Orlando, Florida, USA
CHEMICAL
INDEXING- print .
15. Mesenchymal
Stem
Cells
as facilitators of Transplantion Tolerance
FRP 02-04
1R21HL69724-01 NDN-
049-0310-1158-7
BARTHOLOMEW, AMELIA M
AGENCY- CRISP
CORPORATE AUTHOR- UNIVERSITY OF ILLINOIS AT CHICAGO
CHICAGO
ILLINOIS
SUPPORT
ORGANIZATION NAME- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
RESEARCHER ADDRESS- UNIVERSITY OF ILLINOIS, RM 402 CSB,
M/C 958, CHICAGO, IL 60612
AWARD TYPE- New Award
(Type 1)
FISCAL YEAR- 2001
DESCRIPTION (provided by applicant): Transplantation tolerance, or
the permanent acceptance of an allograft without the need for chronic
immunosuppression, has remained clinically elusive. Strategies to induce
tolerance through the production of lymphohematopoietic chimerism, though
successful in small and large animal models, have been hampered by the
toxicities involved in conditioning the recipient. Host conditioning
regimens have traditionally required elements to eliminate or inactivate
host-alloreactive T cells and cytoreductive treatment to liberate niches
within the bone marrow microenvironment for allogeneic engraftment. Recent
advances in stem cell biology have provided data indicating the requirement
for cytotoxic therapy can be overcome by using very large doses of HSCs.
Possible explanations of this observation have included improved
competition of donor stem cells for marrow niches and diminished
frequencies of cytotoxic T lymphocyte precursors by the direct interaction
with hematopoietic stem cells. A component of the bone marrow that has
largely been ignored and is poorly understood, is the MSC. These stromal
elements, occurring in very low frequency, are multipotential cells that
can be induced to differentiate into bone, muscle, adipocytes, myocytes,
and brain and share many functional and phenotypical characteristics of
thymic stromal cells. Further, they can provide regulatory signals that
inhibit or promote lympho- and myelopoiesis, differentiation, and
proliferation and secrete potent molecules, such as TGF-beta, SDF-1, IL-7,
and FGF that affect T and B cell migration. Interestingly, the
transplantation of bone fragments for stromal microenvironment in
conjunction with HSCs has led to increased hematopoietic engraftment and
transplantation tolerance. We have shown that transplantation of the bone
marrow microenvironment without HSCs can also lead to the permanent
acceptance of murine cardiac allografts. The separate contributions of bone
and MSCs in these observations are unknown. Our preliminary studies suggest
that MSCs can inhibit T cell proliferation in the mixed lymphocyte
reaction, prolong skin graft survival in baboons, and home to the baboon
bone marrow compartment, thereby potentially influencing the host
microenvironment. These observations have led us to hypothesize that MSCs
have immunomodulatory properties and play a major role in the induction of
transplantation tolerance. The first specific aim will test the ability of
mouse MSCs to engraft in the bone marrow and thymic microenvironments and
to alter host T cell repertoire. The mechanism of effect on the host immune
system will be explored to determine whether MSCs directly affect host T
cells or whether MSCs induce a CD8 autoregulatory subset in the host.
Specific aim 2 will test whether MSCs can function as facilitators of HSC
engraftment in lethally irradiated mice. We will also test whether MSCs can
eliminate the need for high dose HSC in minimally conditioned mice.
Insights gained on the role donor MSCs play in allograft acceptance may
then be applied to our pre-clinical baboon model for development of novel
pre-clinical cellular therapies in transplantation tolerance.
DESCRIPTOR(S)- BONE MARROW; CELLULAR
IMMUNITY;
HEART
TRANSPLANTATION
; HEMATOPOIETIC
STEM
CELL
;
HISTOCOMPATIBILITY; HOMOLOGOUS
TRANSPLANTATION
; IMMUNE TOLERANCE
/UNRESPONSIVENESS; IMMUNOSUPPRESSION; LABORATORY MOUSE; POLYMERASE CHAIN
REACTION;
STEM
CELL
; T LYMPHOCYTE;
TRANSPLANTATION
IMMUNOLOGY .
16. Role of
Cell Grafting and Angiogenesis in Infarct Repair
FRP 02-04
1F32HL68400-01 NDN-
049-0310-0958-1
MINAMI, ELINA
AGENCY- CRISP
CORPORATE AUTHOR- UNIVERSITY OF WASHINGTON
SEATTLE
WASHINGTON
SUPPORT
ORGANIZATION NAME- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
RESEARCHER ADDRESS- 2415 2ND AVE., #436, 2415 2ND AVE.
#436, SEATTLE, WA 98121
AWARD TYPE- New Award
(Type 1)
FISCAL YEAR- 2001
DESCRIPTION (Provided by Applicant): The main objective of this
grant is to minimize infarct expansion and to understand how left
ventricular dilatation can be attenuated. The overall hypothesis of this
proposal is that cellular and molecular interventions during infarct repair
will improve post-infarct remodeling and thereby improve cardiac
contractile function. By using an animal model, we will address the
following specific aims: 1) to determine how remodeling is altered by
skeletal muscle and fibroblast grafting 2) to determine if accelerating
granulation tissue formation using growth factors i.e. VEGF and bFGF will
alter remodeling 3) to determine if endothelial progenitor cell grafting
can accelerate granulation tissue formation and alter remodeling. By
engrafting skeletal muscle and fibroblast cells to the infarcted wall of
rats, we will determine how they improve overall ventricular contractility.
The remodeling process and its effect on ventricular function will be
evaluated using echocardiography, left heart catheterization, morphometric
measurements, and histology. In two separate experiments, we will
accelerate granulation tissue formation. The first experiment will use VEGF
and bFGF to create angiogenesis and limit infarct expansion in rat
infarcts. Angiogenesis will be quantified using radioactive microspheres.
The second will utilize the Tie2/LacZ mouse. Endothelial progenitor cells
from these mice will be injected to the infarcted wall to create de-novo
vessel formation, which will stain blue on histology.
DESCRIPTOR(S)- ANGIOGENESIS;
CARDIOVASCULAR DISORDER THERAPY; ECHOCARDIOGRAPHY; FIBROBLAST;
FIBROBLAST GROWTH FACTOR;
HEART
CELL;
HEART
FUNCTION; HEMODYNAMICS;
LABORATORY MOUSE; LABORATORY RAT;
MYOBLAST
; MYOCARDIAL INFARCTION;
NONHUMAN THERAPY EVALUATION;
STEM
CELL
TRANSPLANTATION
; STRIATED
MUSCLE; VASCULAR ENDOTHELIAL GROWTH FACTOR; VASCULAR ENDOTHELIUM
.
17.
Stem
Cell
Therapy and Postinfarction LV Remodeling
FRP 02-04
1R01HL67828-01 NDN-
049-0310-0798-5
ZHANG, JIANYI
AGENCY- CRISP
CORPORATE AUTHOR- UNIVERSITY OF MINNESOTA TWIN CITIES
MINNEAPOLIS
MINNESOTA
SUPPORT ORGANIZATION NAME- NATIONAL HEART, LUNG, AND BLOOD
INSTITUTE
RESEARCHER ADDRESS- UNIVERSITY OF
MINNESOTA, 420 DELAWARE STREET SE, MINNEAPOLIS, MN 55455
AWARD TYPE- New Award (Type 1)
FISCAL
YEAR- 2001
DESCRIPTION (provided by applicant): One of the important
unresolved issues in physiological shock is understanding the mechanism
leading to formation of an inflammatory cascade. Shock is accompanied by
cell activation in the microcirculation, leukocyte infiltration, cell
dysfunction, apoptosis and organ failure. We recently obtained evidence
that pancreatic enzymes serve as a powerful source for generation of
humoral inflammatory mediators in the ischemic intestine. Blockade of
pancreatic enzymes in the lumen of the ischemic intestine leads to high
levels of protection against inflammation and multi-organ failure. Our
results point to an important role for pancreatic serine proteinases. In
accordance with this evidence we hypothesize that pancreatic digestive
enzymes in the intestine can escape across the brush border cell barrier
during ischemia and thereafter produce humoral inflammatory mediators by
digestion of extracellular matrix proteins and other cellular components.
Our Specific Aims are (1) to identify specific pancreatic enzyme activities
which contribute to humoral microvascular activator production in
hemorrhagic shock by enzyme blockade in the lumen of the ischemic intestine
and by introduction of purified pancreatic enzymes into the lumen of the
small intestine; (2) to examine the pancreatic enzyme localization in the
tissue before and after intestinal ischemia and determine the production of
inflammatory mediator production in the interstitial space of the small
intestine; (3) to examine molecular mechanisms for initiation of
inflammation in a peripheral organ after activator production by pancreatic
enzymes in the intestine; and (4) to purify and characterize selected
inflammatory mediators produced by pancreatic enzymes from homogenates of
pancreas as an ubiquitous source of inflammatory mediators and from digests
of purified extracellular matrix proteins (including fibronectin,
vitronectin, and collagen I, III and IV) with serine proteinases. We will
study, using state of the art digital in-vivo microscopy, transport and
action of pancreatic enzymes in combination with biochemical identification
of inflammatory mediators in the rat shock model. Biochemical
identification of the inflammatory mediators is facilitated by availability
of large quantities of starting material from harvested rat and pig
pancreatic tissue. Understanding the trigger mechanisms for inflammation in
shock will lead to new treatment modalities in man.
DESCRIPTOR(S)- BIOENERGETICS; CARDIAC
MYOCYTE; CELL DIFFERENTIATION; CONGESTIVE
HEART
FAILURE;
HEART
FUNCTION;
HEART
METABOLISM; MAGNETIC RESONANCE IMAGING; MYOCARDIAL
INFARCTION; NONHUMAN THERAPY EVALUATION; NUCLEAR MAGNETIC RESONANCE
SPECTROSCOPY; REGENERATION;
STEM
CELL
;
STEM
CELL
TRANSPLANTATION
; SWINE .
18. Potential
of blood progenitors to form nonblood tissue
FRP 02-04
1R21HL66055-01A1 NDN-
049-0310-0174-0
EISENBERG, CAROL A
AGENCY- CRISP
CORPORATE AUTHOR- MEDICAL UNIVERSITY OF SOUTH CAROLINA
CHARLESTON
SOUTH CAROLINA
SUPPORT ORGANIZATION NAME- NATIONAL HEART, LUNG, AND BLOOD
INSTITUTE
RESEARCHER ADDRESS- MED UNIV OF SOUTH
CAROLINA, 173 ASHLEY AVE, STE 652, CHARLESTON, SC 29425-2204
AWARD TYPE- New Award (Type 1)
FISCAL
YEAR- 2001
DESCRIPTION (provided by applicant): A dynamic area in
biotechnology today is stem cell research. Stem cells are the precursor
cells of every tissue in the body and thus, have the potential to provide
replacement tissue for diseased and damaged organs. Our studies on stem
cell differentiation suggest that adult and embryonic stem cells share a
similar tissue potential. Specifically, we believe that stem cells from
adult mammalian bone marrow have the capacity to give rise to all mesoderm
derived tissue-although this potential is never realized in the normal
adult environment. Initial studies have shown, for example, that
hematopoietic stem cells (HSCs) from adult bone marrow-which normally give
rise to the cellular components of the blood-can develop into cardiac
myocytes under conditions developed for nondifferentiated embryonic tissue
to undergo cardiac differentiation. As a first demonstration of our
hypothesis on the broad potential of adult stem cells, we propose to
extensively study the formation of cardiac tissue from adult mouse bone
marrow stem cells. The experiments outlined in this project are designed
to: (I) definitively identify this cardiac competent cell population of the
bone marrow, (II) examine the capacity of this bone marrow cellular
subpopulation to maintain their cardiac competence following their
expansion in culture, (Ill) investigate their capabilities as cardiac
cells, and (IV) examine their ability to integrate into adult cardiac
tissue as functional cardiomyocytes. The development of methods to
manipulate stem cell potential will have significant future medical impact,
as it will provide the means to convert stem cells to pure populations of
individual cell types for replacement tissue.
DESCRIPTOR(S)- BONE MARROW; CARDIAC
MYOCYTE; CARDIOVASCULAR FUNCTION; CELL DIFFERENTIATION; CELL POPULATION
STUDY; CELL PROLIFERATION; CELL
TRANSPLANTATION
; CYTOLOGY; GENE
EXPRESSION;
HEART
CELL;
HEART
SURGERY; HEMATOPOIETIC
STEM
CELL
;
HOMOLOGOUS
TRANSPLANTATION
; IMMUNOCYTOCHEMISTRY; LABORATORY MOUSE;
MATURE ANIMAL; MESODERM; PHENOTYPE; PLURIPOTENT
STEM
CELL
;
POLYMERASE CHAIN REACTION; TISSUE /CELL CULTURE; TRANSMISSION ELECTRON
MICROSCOPY .
19. AUGMENTING
MYOCARDIAL REGENERATION THROUGH ANGIOGENESIS
FRP 02-04
5R01HL63703-02 NDN-
049-0309-9400-9
TAYLOR, DORIS A
AGENCY- CRISP
CORPORATE AUTHOR- DUKE UNIVERSITY
DURHAM
NORTH CAROLINA
SUPPORT ORGANIZATION
NAME- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
RESEARCHER ADDRESS- DUKE UNIVERSITY MEDICAL CENTER, BOX 3345,
DURHAM, NC 27710
AWARD TYPE- Noncompeting
Continuation (Type 5)
FISCAL YEAR- 2001
DESCRIPTION (Adapted from Applicant's Abstract): A potential role
for skeletal myoblast transplantation (cellular cardiomyoplasty) in
augmenting myocardial performance in disease states is established. Yet, a
number of factors continue to limit myoblast engraftment and thus
performance. For example, reduced substrate delivery and toxin removal may
limit myoblast therapy. Data also support the role of therapeutic
angiogenesis (increased vascular density) in augmenting some aspects of
myocardial performance. However, increasing vascular density in the absence
of viable target tissue is likely to yield less than optimal benefit.
Combining CCM and therapeutic angiogenesis may allow optimal benefit from
both regimens, beyond a simple additive effect. The investigators
hypothesize that relative ischemia, in the setting of myocardial
infarction, limits transplanted skeletal myoblast growth and endgraftment
within damaged heart. Therefore, increasing vascular density and blood flow
in injured myocardium may augment myoblast engraftment and thereby improve
myocardial performance. Timing of this increase in blood flow relative to
myoblast injection is likely to be critical. Although increased vascular
density and blood flow alone may increase myocardial compliance, a greater
impact (especially on systolic performance or myocardial contractility) is
likely to derive from combined treatment with myoblast transplantation. The
aims designed to test this hypothesis are to: 1) Increase vascular density
within damaged myocardium 7 - 10 days prior to skeletal myoblast
transplantation and determine the effect on vascularity (in vivo blood
flow, regional capillary density, VEGF, FGF protein expression), and scar
histology (scar size, cardiocyte or myoblast apoptosis, myoblast
proliferation and percent myoblast engraftment). 2) increase vascular
density within damaged myocardium shortly after myoblast delivery (by
injecting myoblasts that over-express secretable VEGF or bFGF) and
ascertaining the effect on vascularity (blood flow, regional capillary
density, VEGF or FGF protein expression); and scar histology (scar size,
cardiocyte or myoblast apoptosis, myoblast proliferation and percent
myoblast engraftment). 3) Increase vascular density within damaged
myocardium (by delivery of angiogenic molecules in the presence or absence
of skeletal myoblast transplantation) and compare the effect on myocardial
performance. Accomplishing these specific aims should enable them to
develop and evaluate novel methods for treating end stage heart disease.
DESCRIPTOR(S)- ANGIOGENESIS;
APOPTOSIS; BLOOD FLOW; BLOOD VISCOSITY; CARDIAC MYOCYTE; CELL
PROLIFERATION; CELL
TRANSPLANTATION
; DISEASE /DISORDER MODEL;
FIBROBLAST GROWTH FACTOR; GENE EXPRESSION;
HEART
CONTRACTION;
HEART
FUNCTION; HISTOLOGY; LABORATORY RABBIT;
MYOBLAST
; MYOCARDIAL
INFARCTION;
MYOCARDIUM
; SCAR; TISSUE /CELL CULTURE; TISSUE
ENGINEERING; VASCULAR ENDOTHELIAL GROWTH FACTOR; VASCULAR
ENDOTHELIUM .
20. SAFETY AND
EFFICACY OF CELLULAR CARDIOMYOPLASTY
FRP
02-04 5R01HL63346-03 NDN- 049-0309-9300-5
TAYLOR, DORIS A
AGENCY- CRISP
CORPORATE AUTHOR- DUKE UNIVERSITY
DURHAM
NORTH CAROLINA
SUPPORT ORGANIZATION
NAME- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
RESEARCHER ADDRESS- DUKE UNIVERSITY MEDICAL CENTER, BOX 3345,
DURHAM, NC 27710
AWARD TYPE- Noncompeting
Continuation (Type 5)
FISCAL YEAR- 2001
Description (Adapted from Applicant's Abstract): The overall goal
of this project is to determine whether autotransplantation of skeletal
myoblasts into scarred or failing myocardium will lead to long term
survival of the myoblast and improvement in systolic and diastolic
contractile function. The Principal Investigator plans to use a model of
cryoablation injury to the ventricle injecting the myoblasts into the area
of damage. In the first aim she will develop a method of labeling the
transplanted cells so that they could be detected late and to facilitate
determination of longevity. In the second aim, she will determine regional
wall motion abnormalities in the area of myoblast transplantation and
determine the microenvironment to which the cells are transplanted. In the
third aim, she will determine whether the viability of harvested skeletal
myoblasts is altered by the presence of congestive heart failure. She will
also test the efficacy of myoblast transplantation in a model of coronary
ischemia.
DESCRIPTOR(S)- AUTOLOGOUS
TRANSPLANTATION
; CELL POPULATION STUDY; CELL
TRANSPLANTATION
;
CONGESTIVE
HEART
FAILURE; CRYOSURGERY; ECHOCARDIOGRAPHY; ELECTRON
MICROSCOPY; ELECTROPHYSIOLOGY; EXTRACELLULAR MATRIX; GAP JUNCTION;
GREEN FLUORESCENT PROTEIN;
HEART
CONTRACTION;
HEART
VENTRICLE;
IMMUNOCYTOCHEMISTRY; MEMBRANE CHANNEL;
MYOBLAST
; MYOCARDIAL
INFARCTION; MYOCARDIAL ISCHEMIA /HYPOXIA;
MYOCARDIUM
; NONHUMAN THERAPY
EVALUATION; REPORTER GENE; TISSUE /CELL CULTURE; TRANSFECTION
/EXPRESSION VECTOR; VASCULAR ENDOTHELIAL GROWTH FACTOR; WESTERN
BLOTTING .
21. EMBRYONIC
ORIGIN OF LYMPHATIC
HEART
MUSCLE
MYOBLASTS
FRP 02-04
1R15HL62616-01 NDN-
049-0309-9112-4
RADICE, GARY P
AGENCY- CRISP
CORPORATE AUTHOR- UNIVERSITY OF RICHMOND
RICHMOND
VIRGINIA
SUPPORT
ORGANIZATION NAME- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
RESEARCHER ADDRESS- UNIVERSITY OF RICHMOND, GOTTWALD
SCIENCE CENTER, RICHMOND, VA 23173
AWARD TYPE- New
Award (Type 1)
FISCAL YEAR- 2001
DESCRIPTION (adapted from investigator's abstract): In addition to
skeletal, smo oth and cardiac muscle, many animals have an unusual muscle
in the beating heart s of the lymphatic system (LHM muscle). Unlike the
three main muscle types, the tissue origin and signals that induce LHM
cells to form have not been studied an d are not known. This project seeks
to discover the origin of LHM by labeling po tential origin tissues and
transplanting them to unlabeled hosts. These studies should reveal the
origin of LHM cells and the origin of signals that may induce their
formation.
DESCRIPTOR(S)- CELL DIFFERENTIATION;
DEVELOPMENTAL GENETICS; DYE; EMBRYO /FETUS; EMBRYO /FETUS TISSUE
TRANSPLANTATION
; LYMPHATIC SYSTEM; MICROINJECTION; MICROSURGERY;
MUSCLE
TRANSPLANTATION
;
MYOBLAST
;
MYOCARDIUM
; NONMAMMALIAN
VERTEBRATE EMBRYOLOGY; XENOPUS .
22. COLLABORATIVE R01
FRP
02-04 5R01HL61624-04 NDN- 049-0309-8765-0
BASSEL-DUBY, RHONDA
AGENCY- CRISP
CORPORATE AUTHOR- UNIVERSITY OF TEXAS SW MED CTR/DALLAS
DALLAS
TEXAS
SUPPORT
ORGANIZATION NAME- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
RESEARCHER ADDRESS- UNIV OF TEXAS SW MED CTR, DALLAS TX
75390-8573
AWARD TYPE- Noncompeting Continuation
(Type 5)
FISCAL YEAR- 2001
DESCRIPTION (Adapted from the applicant's abstract) Current
therapeutics applied to patients with heart failure, with the exception of
cardiac transplantation, fail to address the quantitative deficiency of
cardiomyocytes that compromises ventricular performance in many of these
individuals. A successful biotechnological strategy to add new
cardiomyocytes to the damaged heart would meet a major clinical need. The
investigators propose to identify or engineer cardiogenic cells that,
following transplantation to the myocardial wall, are capable of
proliferation, differentiation, and correct pattern formation in a manner
sufficient to improve cardiac function. The approach is novel, systematic
and multidisciplinary, and will be constructed upon an expanding foundation
of new knowledge concerning molecular mechanisms of cardiogenesis in
mammalian and amphibian embryos, and of myogenic repair in adult skeletal
muscles. The experimental plans have been designed to take maximum
advantage of emerging technologies and powerful model systems. The
participating investigators have expertise in diverse areas of science
relevant to this research including biophysics, developmental biology,
molecular genetics, and clinical cardiology, but they work within a single
institution and this joint proposal is enhanced by pre-existing and ongoing
scientific relationships. The investigators propose to gain, in parallel, a
more detailed understanding of the biology of skeletal myogenic stem cells
(satellite cells) and how they contrast with myogenic precursor cells
(cardioblasts) from the developing heart, specifically in the context of
tissue regeneration. Putative cardiogenic cells will be isolated from early
embryos or from embryoid bodies in culture, or engineered by
transdifferentiation of skeletal myogenic cells. Each candidate cell type
will be characterized comprehensively with respect to its repertoire of
expressed genes, and its capacity to promote effective cardiogenic tissue
repair following transplantation into ectopic locations or into the
myocardial wall of cardiomyopathic animals. Each round of testing will be
followed by the application of enhancing strategies, chosen on the basis of
results acquired from preceding analyses within each of the separate
components of this proposal, and designed to optimize the tissue repair
process. In this iterative manner, the investigators expect to gain
knowledge that ultimately will foster the development of cell
transplantation strategies to promote myocardial repair in human patients
afflicted with heart failure.
DESCRIPTOR(S)- CARDIAC MYOCYTE; CELL
DIFFERENTIATION; CELL PROLIFERATION; CELL
TRANSPLANTATION
; COOPERATIVE
STUDY; EMBRYO /FETUS;
HEART
CELL; LABORATORY MOUSE; MUSCLE CELL;
MUSCLE SATELLITE CELL;
MYOBLAST
;
MYOCARDIUM
; REGENERATION; TISSUE
/CELL CULTURE; TISSUE ENGINEERING; TRANSGENIC ANIMAL
.
23. CARDIAL
GRAFTS--FETAL AND ES DERIVED DONOR CELLS
FRP
02-04 5R01HL61622-04 NDN- 049-0309-8764-9
FIELD, LOREN J
AGENCY- CRISP
CORPORATE AUTHOR- INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
INDIANAPOLIS
INDIANA
SUPPORT ORGANIZATION NAME- NATIONAL HEART, LUNG, AND BLOOD
INSTITUTE
RESEARCHER ADDRESS- INDIANA UNIVERSITY,
1111 WEST 10TH STREET, INDIANAPOLIS, IN 46202-4800
AWARD TYPE- Noncompeting Continuation (Type 5)
FISCAL YEAR- 2001
DESCRIPTION (Adapted from the applicant's abstract) Cardiomyocyte
death is a common feature of many forms of heart disease. Since the
myocardium lacks a substantive endogenous regenerative potential,
cardiomyocyte death is essentially irreversible. It has recently become
apparent that exogenous myocytes can be successfully engrafted into the
adult myocardium, thereby increasing the number of cells present in the
heart. This procedure may be of considerable therapeutic value if engrafted
cells can augment function in a diseased heart. Indeed, strategies aimed at
increasing myocyte number was viewed with the highest priority by the NHLBI
Special Emphasis Panel on Heart Failure Research and by this RFA. However,
several rather formidable issues and obstacles must be addressed before any
therapy based on myocyte engraftment can he realized. The five highly
integrated Collaborative R01s proposed herein are designed to directly
address these issues. A major goal of the proposed studies is to establish
the fate of donor cells following engraftment. Particular emphasis is being
placed on identifying factor(s) which enhance donor cell viability (Dr.
Kedes), and on determining the degree to which donor and host myocytes can
interact (Field and Murry). Other studies (Field, Murry, Kedes and
Hauschka) will establish the relative merits of a variety of different
donor cells (fetal cardiomyocytes, skeletal myo-blasts, ES- and EC-derived
cardiomyocytes, and smooth muscle cells). Particular emphasis will be
placed on weighing the issue of donor cell availability versus the
functional characteristics of their respective grafts. Functional analyses
of the engrafted hearts will rely largely on highly sensitive 2D
echocardiography (KIoner). These latter studies will also establish to what
degree cellular engraftment has a direct versus indirect effect on cardiac
function (that is, participation in contractile force generation versus a
positive effect on remodeling). The assembled investigators have
established track records in relatively new field of cardiac engraftment,
and additionally bring a diverse spectrum of experimental expertise which
collectively provide a comprehensive battery of molecular, cellular and
functional experimental methods. (End of Abstract)
DESCRIPTOR(S)- CARDIAC MYOCYTE; CELL
CELL INTERACTION; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL
TRANSPLANTATION
; CONFOCAL SCANNING MICROSCOPY; DOG; ECHOCARDIOGRAPHY;
EMBRYO /FETUS CELL /TISSUE; EMBRYONIC
STEM
CELL
;
HEART
CONTRACTION;
HEART
FUNCTION; HYPERTROPHY; IN SITU HYBRIDIZATION; LABORATORY MOUSE;
LABORATORY RAT; MIXED TISSUE /CELL CULTURE;
MYOCARDIUM
; NORTHERN
BLOTTING; POLYMERASE CHAIN REACTION; POSTOPERATIVE STATE; RESTRICTION
FRAGMENT LENGTH POLYMORPHISM; SMOOTH MUSCLE; TRANSCRIPTION FACTOR;
WESTERN BLOTTING .
24. DEVELOPING
CELLULAR CARDIOMYOPLASTY FOR INJURED
HEART
FRP 02-04
5R01HL57988-05 NDN-
049-0309-7721-8
TAYLOR, DORIS A
AGENCY- CRISP
CORPORATE AUTHOR- DUKE UNIVERSITY
DURHAM
NORTH CAROLINA
SUPPORT ORGANIZATION
NAME- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
RESEARCHER ADDRESS- DUKE UNIVERSITY MEDICAL CENTER, BOX 3327,
DURHAM, NC 27710
AWARD TYPE- Noncompeting
Continuation (Type 5)
FISCAL YEAR- 2001
Because the adult heart cannot regenerate or repair itself, the end
result of ischemic heart disease (IHD) is often progression of acute
myocardial infarction (AMI) to congestive heart failure (CHF) resulting in
the death of over 41,000 persons annually. Currently, medical interventions
to prevent the progression to heart failure following a severe AMI are
limited. Treatment options for end-stage CHF are even more limited. A new
therapeutic option in development, cellular cardiomyoplasty (CCM), or
transplantation of autologous primary skeletal muscle cells into the
myocardium, offers potential for augmenting cardiac function in myocardial
disease. The overall aim of this project is to develop a basis for the use
of cellular cardiomyoplasty in cardiac disease including AMI and CHF. The
hypothesis is: in a rabbit model of myocardial infarction, decreased
myocardial performance can be at least partly reversed by repopulating the
damaged area with primary skeletal myoblasts to re- form a functional unit
within an infarct region. The specific aims to test this hypothesis are to:
1) optimize marker gene expression in autologous primary skeletal muscle
myoblasts to follow their fate in the heart; 2) compare the efficiency of
tow methods of myoblast delivery to rabbit heart: localized delivery via
direct injection or more dispersed delivery via infusion onto the coronary
circulation; 3) use load-insensitive in dices of regional cardiac function
to determine the temporal effects of directly injected myoblasts on
regional contractile function and on ventricular morphology in control and
infarcted hearts; 4) determine the temporal effects of myoblasts infused
into the coronary circulation on global contractile function (by 2-d
echocardiography) and ventricular morphology in control and infarcted
hearts. Accomplishing these aims should allow an evaluation of the extent
to which autologus skeletal myoblasts can survive implantation into the
cardiac environment and contribute to cardiac function. Developing cellular
cardiomyoplasty may contribute a promising therapeutic intervention for IHD
or CHF both of which are major economic and management problems for all
health care providers because of the substantial health care costs expended
in the treatment of these severely debilitating conditions and because of
the limitations of definitive therapeutic interventions. R02MH49428 There
is abundant evidence to suggest that neuropsychiatric disorders such as
schizophrenia and autism are caused in many cases by genetic abnormalities
that affect development and function of forebrain neural systems involved
in cognition and emotion. The largest structures of the forebrain are the
cerebral cortex and the striatum; both have been implicated as having a
role in neuropsychiatric disorders. The goal of my research is to
understand how genes regulate development of the striatum. To this end, my
laboratory has identifies the D1x genes, which encoded a family of
homeodomain transcription factors that are candidates for having a central
role in striatal development. There are four known D1x genes that are
expressed in the embryonic forebrain. The aims of the experiments proposed
in this grant application are focused on: (1) elucidating the sequence of
these genes and their encoded proteins; (2) characterizing the biochemical
properties of the DLX proteins; (3) determining whether the DLX proteins
are transcriptional regulators; (4) identifying proteins that interact with
and modulate the function of the DLX proteins; (5) determining the
intracellular location of the DLX proteins; (6) determining the temporal
and spatial patterns expression of the D1x RNAs and proteins in the
prenatal and postnatal forebrain; (7) begin to determine where the D1x
genes are in the genetic hierarchy that regulates development of the
forebrain using ectopic expression experiments.
DESCRIPTOR(S)- ADENOVIRIDAE;
AUTOLOGOUS
TRANSPLANTATION
; BETA GALACTOSIDASE; BIOENGINEERING
/BIOMEDICAL ENGINEERING; BIOTECHNOLOGY; CELL
TRANSPLANTATION
; DISEASE
/DISORDER MODEL; ECHOCARDIOGRAPHY; ELECTRON MICROSCOPY; GENE EXPRESSION;
GENETIC MARKER; GENETIC TRANSDUCTION;
HEART
CIRCULATION;
HEART
CONTRACTION; IMMUNOCYTOCHEMISTRY; IMPLANT;
INJECTION
/INFUSION;
INTRAARTERIAL ADMINISTRATION; LABORATORY RABBIT; METHOD DEVELOPMENT;
MYOBLAST
; MYOCARDIAL INFARCTION;
MYOCARDIUM
; RETROVIRIDAE; STRIATED
MUSCLE; TRANSFECTION /EXPRESSION VECTOR .
25. Adult
Stem
Cell
Therapy For Cardiac Failure
FRP
02-04 1Z01HL05057-01 NDN- 049-0309-4633-7
EPSTEIN, NEAL D
AGENCY- CRISP
SUPPORT ORGANIZATION NAME- NATIONAL HEART, LUNG, AND BLOOD
INSTITUTE
RESEARCHER ADDRESS- NHLBI, NIH
AWARD TYPE- Not Applicable
FISCAL
YEAR- 2001
Heart failure may occur from a variety of causes including ischemic
heart diseas e, toxins, pressure or volume overload. Recovery of cardiac
function is hindered by a long known observation that cardiac myocytes do
not divide in appreciable numbers during adult life. Physiologic demands
for increased cardiac output are met by hypertrophy of existing cardiac
myocytes through the formation of additio nal sarcomeres (the unitary
contractile apparatus)within these cells. At the pre sent time, the only
remedy for end stage heart failure is cardiac transplant, wh ich is limited
by the supply of matched hearts and complicated by the need to su ppress
immune rejection. We have discovered a previously unknown subpopulation o f
stem cells in adult murine skeletal muscle that can be transformed into
beatin g cardiomyocytes under primary tissue culture conditions. These
cells are not sa tellite cells, myofibroblasts or myoblasts. A portion of
the freshly isolated st em cells, injected into the vein of a mouse with
chronic heart failure, will hom e to the heart and progress along a pathway
to cardiac cell differentiation. In addition, we have produced a
conditioned media from co-cultured bone-marrow and skeletal muscle cells
that shortens the time that it takes the isolated stem cel ls to
differentiate into cardiac myocytes. We are presently using a variety of g
ene array, genetic subtraction and immunologic techniques to further
characteriz e these cells in order to facilitate the identification of
human analogues. If t he latter can be identified and isolated, they may be
useful for therapeutic int ervention in cardiac failure from a variety of
causes. This would avoid the prob lems of immune rejection as well as the
supply limitations of organ
DESCRIPTOR(S)- BONE MARROW;
CARDIOVASCULAR DISORDER THERAPY;
HEART
FAILURE;
HEART
FUNCTION;
IMMUNOLOGIC TECHNIQUE; LABORATORY MOUSE; MATURE ANIMAL; MICROARRAY
TECHNOLOGY; MIXED TISSUE /CELL CULTURE; MUSCLE CELL;
MYOBLAST
;
STEM
CELL
TRANSPLANTATION
; STRIATED MUSCLE; SUBTRACTION HYBRIDIZATION;
TRANSPLANT
REJECTION .
26. MYOCARDIAL
INFARCT REPAIR
FRP 02-04
5P01HL03174-46 0027 NDN-
049-0309-4051-7
MURRY, CHARLES E
AGENCY- CRISP
CORPORATE AUTHOR- UNIVERSITY OF WASHINGTON
SEATTLE
WASHINGTON
SUPPORT
ORGANIZATION NAME- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
RESEARCHER ADDRESS- UNIVERSITY OF WASHINGTON, UNIVERSITY
OF WASHINGTON, SEATTLE, WA 98195
AWARD TYPE-
Noncompeting Continuation (Type 5)
FISCAL YEAR-
2001
Myocardial infarcts heal by scarring because cardiocytes cannot
replicate after injury, and because there are no muscle stem cells in the
heart. Previous studies showed that MyoD gene transfer or skeletal myoblast
grafting can form new contractile tissue in injured hearts, but that
skeletal muscle does not form electromechanical junctions with surrounding
myocardium. The goals of this project are 1) to develop strategies to
repair infarcts with muscle that integrates electrically and mechanically
with the remaining myocardium; and 2) to understand how cardiac wound
healing is normally regulated to permit rational design of therapies to
enhance infarct repair. Specific Aim 1 will determine whether cardiac
myocytes from developing or adult hearts can be grafted into injured adult
hearts. Physiological studies will determine if cardiocyte grafting
improves regional contractile function in vivo. In Specific Aim 2, skeletal
myoblasts will be genetically modified to express N-cadherin and connexin
43, the principal proteins of cardiac adherens and gap junctions,
respectively. Co-cultures of cardiocytes and transfected skeletal muscle
will be studied structurally and functionally for adherens and gap
junction. In vivo studies will determine if the genetically modified cells
integrate into host myocardium and restore regional contractile function
after injury. Specific Aim 3 focuses on the role of osteopontin, a matrix
adhesive protein highly expressed by macrophages, in cardiac wound repair.
We will administer anti-osteopontin antibodies to rats with cardiac injury
and also study cardiac repair in osteopontin- deficient mice. Cell culture
studies will determine if osteopontin promotes phagocytosis by macrophages
or adhesion and migration of cardiac fibroblasts. In Specific Aim 4 we will
study the time course of growth factor (bFGF, VEGF, PDGF, TGF-beta)
production following cardiac injury to identify candidate mitogens.
Individual growth factors will be studied by administering recombinant
molecules systematically and through the use of blocking antibodies in rats
with healing infarcts.
DESCRIPTOR(S)- CADHERIN; CARDIAC
MYOCYTE; CELL GROWTH REGULATION; CELL MIGRATION; CELL
TRANSPLANTATION
;
GAP JUNCTION; GROWTH FACTOR;
HEART
CONTRACTION; HISTOPATHOLOGY;
LABORATORY MOUSE; LABORATORY RAT; MACROPHAGE; MITOGEN; MIXED TISSUE
/CELL CULTURE; MUSCLE
TRANSPLANTATION
;
MYOBLAST
; MYOCARDIAL
INFARCTION;
MYOCARDIUM
; MYOGENESIS; OSTEOPONTIN; PHAGOCYTOSIS;
TISSUE ENGINEERING; TRANSFECTION; WOUND HEALING .
27. Gene
Transfer And Ex Vivo Manipulation Of Hematopoietic
FRP 02-04
1Z01HL02339-10 NDN-
049-0309-4028-1
DUNBAR, CYNTHIA E
AGENCY- CRISP
SUPPORT ORGANIZATION NAME- NATIONAL HEART, LUNG, AND BLOOD
INSTITUTE
RESEARCHER ADDRESS- NHLBI, NIH
AWARD TYPE- Not Applicable
FISCAL
YEAR- 2001
Clinical and basic laboratory studies are directed at developing
efficient and s afe gene transduction and ex vivo manipulation strategies
for hematopoietic cell s, including stem and progenitor cells and
lymphocytes, and using genetic markin g techniques to answer important
questions about in vivo hematopoiesis. In the r hesus model, shown to be
the only predictive assay for human clinical results, w e have focused on
optimizing gene transfer to primitive stem and progenitor cell s, and using
genetic marking techniques to understand stem cell behavior in vivo .We
have continued to further enhance gene transfer efficiency into rhesus
engra fting cells, resulting in early levels of marked cells as high as
50-80%, with s table levels of 5-35% in all lineages, a range with clinical
utility. We have fo und that actively-cycling transduced cells have an
engraftment defect that can b e corrected by a short culture on a
fibronectin fragment with stem cell factor a lone. The high levels have
allowed us to continue to track the clonal contributi ons to hematopoiesis
for the first time in a large animal model. We have continu ed to use
inverse PCR, but have also developed a new technology that allows simu
ltaneous assessment of multiple clonal contributions to peripheral blood
populat ions. We have found a different population of engrafting cells that
contribute f or the first 1-2 months post-transplantation, that are then
replaced by a very s table set of over 80 clones that contribute to all
lineages now for over 3 years . We have begun to investigate the impact of
cytokine therapy, radiation, and ch emotherapy on the in vivo behavior of
stem cell clones, using this powerful meth odology. We have also begun to
study the contributions of these clones to other tissues, including
endothelium and muscle, and have begun to investigate whether stem cell
mobilized by cytokine treatment can contribute to regeneration of myo
cardium following infarction in the primate model.
DESCRIPTOR(S)- BLOOD DISORDER
CHEMOTHERAPY; CELL POPULATION STUDY; GENE THERAPY; GENETIC MARKER;
HEMATOPOIESIS; HEMATOPOIETIC TISSUE TRANSPLANTATIONHEMATOPOIETIC
STEM
CELL
; HUMAN TISSUE; IMMUNOTHERAPY; MACACA MULATTA;
MYOCARDIUM
;
NONHUMAN THERAPY EVALUATION; RADIATION THERAPY; REGENERATION;
RETROVIRIDAE;
STEM
CELL
TRANSPLANTATION
; TISSUE /CELL CULTURE
.
28. LATE
EFFECTS IN SURVIVORS OF
STEM
CELL
TRANSPLANTATION
FRP 02-04
1K23CA85503-01A1 NDN-
049-0306-6857-0
BAKER, KEVIN S
AGENCY- CRISP
CORPORATE AUTHOR- UNIVERSITY OF MINNESOTA TWIN CITIES
MINNEAPOLIS
MINNESOTA
SUPPORT ORGANIZATION NAME- NATIONAL CANCER INSTITUTE
RESEARCHER ADDRESS- UNIV OF MINNESOTA, 420 DELAWARE ST
SE/BOX 484 MAY, MINNEAPOLIS, MN 55455
AWARD TYPE-
New Award (Type 1)
FISCAL YEAR- 2001
DESCRIPTION: (Applicant's Description) K. Scott Baker, M.D. is a
pediatric oncologist in the Blood and Marrow Transplant Program at the
University of Minnesota, and holds an appointment as an Assistant Professor
in the Department of Pediatrics. The candidates career goals are: 1) to
develop clinical research expertise which has a solid foundation in
clinical research methodology, epidemiology, and biostatistics, 2) to focus
these activities on patient oriented research in the field of hematopoietic
stem cell transplantation (SCT), specifically transplant related
complications and late effects, 3) to utilize these newly acquired skills
in order to achieve the status as an independent clinical investigator. The
proposed career development plan will provide a comprehensive,
multidisciplinary, closely mentored, patient oriented research experience.
This will be accomplished in conjunction with formal didactic training in
Clinical Research obtained by the candidate enrolling in the master's
degree program in clinical research in the Division of Epidemiology. Under
the mentorship of Dr. Leslie Robison and Dr. Norma Ramsay, the candidate
will initiate investigations into the late effects seen in long-term
survivors after SCT. The proposed research will establish prospective and
retrospective, long-term follow-up studies of SCT survivors at the
University of Minnesota for the systematic, protocol driven, evaluation of
the incidence, risk factors, and characteristics of cardiopulmonary, renal,
endocrine and reproductive late effects, quality of life outcomes, and
second malignant neoplasms. Hypothesis driven investigations will also be
undertaken in the current population of 1226 long-term survivors. These
will include studies of the impact of different transplant conditioning
regimens (total body irradiation, total lymphoid irradiation, and
chemotherapy only) on subsequent late effects in children, an analysis of
the spectrum and severity of treatment related sequelae which develop in
the second decade of long-term follow-up, and an analysis of the impact
that chronic graft-versus-host disease has on late effects and quality of
life in SCT survivors. The candidate will also utilize data frorn the
ongoing, multi-institutional, Childhood Cancer Survivor Study (Dr. Robison
is Principal Investigator) for a comparative analysis of patients in that
cohort receiving standard chemotherapy versus those who have undergone SCT
as part of their therapy.
DESCRIPTOR(S)- APLASTIC ANEMIA;
CANCER RISK; GRAFT VERSUS HOST DISEASE; HEALTH BEHAVIOR;
HEART
FUNCTION; HEMATOPOIETIC TISSUE TRANSPLANTATIONFERTILITY; HUMAN MORTALITY;
HUMAN SUBJECT; HUMAN THERAPY EVALUATION; IMMUNOPATHOLOGY; METABOLISM
DISORDER; NEOPLASM /CANCER; NEOPLASM /CANCER CHEMOTHERAPY; NEOPLASM
/CANCER GENETICS; NEOPLASM /CANCER RADIATION THERAPY; OUTCOMES RESEARCH;
PATIENT ORIENTED RESEARCH; QUALITY OF LIFE; RADIATION IMMUNOSUPPRESSION;
RESPIRATORY FUNCTION;
STEM
CELL
TRANSPLANTATION
.
29. PATHOGENESIS AND TREATMENT OF CHRONIC REJECTION
FRP 02-04
5R01AI38899-04 NDN-
049-0305-3542-8
MURASE, NORIKO
AGENCY- CRISP
CORPORATE AUTHOR- UNIVERSITY OF PITTSBURGH AT PITTSBURGH
PITTSBURGH
PENNSYLVANIA
SUPPORT ORGANIZATION NAME- NATIONAL INSTITUTE OF ALLERGY AND
INFECTIOUS DISEASES
RESEARCHER ADDRESS- UNIVERSITY
OF PITTSBURGH MED C, 200 LOTHROP STREET, PITTSBURGH, PA 15213
AWARD TYPE- Noncompeting Continuation (Type 5)
FISCAL YEAR- 2001
DESCRIPTION (Adapted from the applicant's abstract): This
investigation postulates that chronic rejection of allografts is caused by
the elimination of donor antigen presenting cells residing in the graft,
and that through retention of these cells, promotes low grade stimulation
of the recipient s immune system leading to prevention of CR. An animal
model as been developed to test this hypothesis. Animals are pretreated
with donor bone marrow or a hepatic allograft in concert with Tacrolimus.
Donor microchimerism persists for at least 100 days, and then, the animals
are challenged with a heterotopic cardiac allograft (CCA). The PI has found
that animals previously receiving a liver allograft do not experience CR
while those that receive bone marrow do. The hypothesis is advanced that
the liver provides the stromal elements for survival of donor hematopoietic
stem cells which protect cardiac allografts from CR. In contrast, with
animals receiving donor bone marrow, there is induction of a strong Th-1
type cell response due to a loss of microchimerism, which leads to CR. In
this project, the PI proposes to study the mechanisms responsible for
lymphocyte trafficking and cellular activation, the influence of persistent
donor antigen presenting cells on the incidence and intensity of CR and
whether maneuvers for augmentation of donor chimerism in human liver
transplant patients lowers the severity of CR.
DESCRIPTOR(S)- ACUTE DISEASE
/DISORDER; ANTIGEN PRESENTING CELL; BONE MARROW
TRANSPLANTATION
;
CHRONIC DISEASE /DISORDER; CLINICAL RESEARCH; DISEASE /DISORDER MODEL;
FK506; FLOW CYTOMETRY;
HEART
TRANSPLANTATION
; HEMATOPOIESIS;
HEMATOPOIETIC
STEM
CELL
; HOMOLOGOUS
TRANSPLANTATION
; HUMAN SUBJECT;
INTERFERON GAMMA; INTERLEUKIN 12; LABORATORY RAT; LEUKOCYTE ACTIVATION
/TRANSFORMATIONIMMUNOCYTOCHEMISTRY; LIVER
TRANSPLANTATION
; MACROPHAGE;
PATHOLOGIC PROCESS; POLYMERASE CHAIN REACTION; PROGNOSIS; TISSUE
MOSAICISM;
TRANSPLANT
REJECTION .
30. Severe
cardiac toxicity in hematological
stem
cell
transplantation
:
predictive value of reduced left ventricular ejection fraction
LSC 01-11
4872268 NDN-
122-0228-3147-1
Fujimaki, K.; Maruta, A.; Yoshida, M.; Sakai, R.; Tanabe, J.;
Koharazawa, H.; Kodama, F.; Asahina, S.; Minamizawa, M.; Matsuzaki, M.;
Fujisawa, S.; Kanamori, H.; Ishigatsubo, Y.
ABBREVIATED JOURNAL TITLE- Bone Marrow
Transplantation ÝBone Marrow Transplant.¨
vol. 27, no. 3,
pp. 307-310
2001-02-01
DOCUMENT
TYPE- Journal Article
BIBLIOGRAPHIC LEVEL-
Analytical, Serial
ISSN- 0268-3369
AUTHOR AFFILIATION- Department of Hematology, Kanagawa Cancer
Center, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan
LANGUAGE- English
Eighty patients receiving hematological stem cell transplantation
(HCT) with a preparative regimen consisting of total body irradiation (12.5
Gy), cyclophosphamide (4000 or 4500 mg/m super(2)), and thiotepa (400 mg/m
super(2)) were evaluated for the development of cardiac toxicity. Patients
in whom the pretransplant cumulative dose of anthracycline was more than or
equal to 300 mg/m super(2) showed a lower left ventricular ejection
fraction (EF) before HCT compared to patients with less than 300 mg/m
super(2) (0.61 plus or minus 0.09 vs 0.67 plus or minus 0.06, P = 0.0010).
Patients who had undergone more than or equal to six courses of
chemotherapy showed a decreased EF before HCT compared to those after less
than six courses (0.67 plus or minus 0.05 vs 0.63 plus or minus 0.09, P =
0.03). Three of seven patients (43%) whose pretransplant EF had been less
than or equal to 0.55 developed severe cardiac toxicity, characterized by
congestive heart failure (CHF) compared with none of 83 patients (0%) whose
pretransplant EF had been more than 0.55 (P = 0.00026). Of the three
patients who developed severe cardiac toxicity, two were given more than
300 mg/m super(2) of cumulative anthracycline and underwent 23 courses and
six courses of chemotherapy, while the other patient received only two
courses of chemotherapy with a total dose of 139 mg/m super(2) of
anthracycline. These results indicate that an increased cumulative dose of
anthracycline and number of chemotherapy treatments are correlated with a
decrease of the EF and that the EF before HCT is useful for predicting the
risk of cardiac complications for recipients who have received
chemotherapy.
DESCRIPTOR(S)- anthracycline;
anthracycline antibiotics; hematological
stem
cell
transplantation
;
stem
cell
transplantation
; thiotepa; Cyclophosphamide;
Heart
;
Immunocompromised hosts; Radiation; Risk assessment;
Stem
cells
;
Transplantation
; Ventricle
IDENTIFIER(S)-
ejection fraction; man; toxicity
SECTIONAL
CLASSIFICATION CODE- 24113, Side effects; 06833, Bone marrow
.
31. Assessment
of cardiotoxicity during haemopoietic
stem
cell
transplantation
with
plasma brain natriuretic peptide
LSC
01-04 4752758 NDN- 122-0221-0761-6
Snowden, J. A.; Hill, G. R.; Hunt, P.; Carnoutsos, S.;
Spearing, R. L.; Espiner, E.; Hart, D. N. J.*
ABBREVIATED JOURNAL TITLE- Bone Marrow
Transplantation ÝBone Marrow Transplant.¨
vol. 26, no. 3,
pp. 309-313
20000801
DOCUMENT
TYPE- Journal Article
BIBLIOGRAPHIC LEVEL-
Analytical, Serial
ISSN- 0268-3369
AUTHOR AFFILIATION- Mater Medical Research Institute, Raymond
Terrace, South Brisbane, Australia
LANGUAGE-
English
Cardiac failure is a known complication of haemopoietic stem cell
transplantation (HSCT) and is often difficult to diagnose as patients may
have multiple medical problems. Since brain natriuretic peptide (BNP) is
largely a hormone of cardiac ventricular origin and is released early in
the course of ventricular dysfunction, we have examined the value of serial
plasma BNP levels for detecting cardiac failure in patients undergoing
cytotoxic conditioning for HSCT. Fifteen patients undergoing HSCT were
evaluated (10 undergoing autologous HSCT; five undergoing allogeneic HSCT).
BNP was measured by radioimmunoassay prior to therapy and weekly for 5
weeks. Seven patients had a significant rise in BNP level (above a
previously established threshold of 43 pmol/l associated with cardiac
failure), occurring 1-4 weeks post commencement of conditioning. In three
of these patients, cardiac failure was subsequently diagnosed clinically 3,
9 and 23 days after a BNP level of 43 pmol/l had been detected. These three
patients had the highest peak BNP levels for the group and in each case
elevation in BNP level occurred for a period exceeding 1 week. Although
numbers were relatively small, a BNP >43 pmol/l was significantly
associated with the inclusion of high-dose cyclophosphamide in the
preparative regimen (P = 0.02). BNP levels showed no relationship to
febrile episodes. In conclusion, these results show that plasma BNP may be
used as a marker for early detection of cardiac dysfunction in patients
undergoing HSCT, particularly if levels are increased for periods exceeding
1 week. Measurement of BNP during HSCT may be helpful in patients at risk
of cardiac failure, in complex clinical situations and in monitoring the
cardiotoxicity of preparative regimens.
DESCRIPTOR(S)- brain natriuretic
peptide;
stem
cell
transplantation
; Bone marrow
transplantation
;
Heart
diseases; Hemopoiesis
IDENTIFIER(S)- man;
toxicity
SECTIONAL CLASSIFICATION CODE- 06833,
Bone marrow .
32. Proliferation switch for skeletal
myoblasts
LSC 01-03
0530446 NDN-
122-0220-9551-1
Whitney, Marsha L.; Otto, Kevin; Blau, C. Anthony; Murry,
Charles E.
ABBREVIATED JOURNAL TITLE- Annals of
Biomedical Engineering ÝAnn Biomed Eng¨
vol. 28, no.
SUPPL. 1, pp. S-119
20000000
DOCUMENT
TYPE- Journal Article
BIBLIOGRAPHIC LEVEL-
Analytical, Serial
ISSN- 0090-6964
AUTHOR AFFILIATION- Univ of Washington, Seattle, WA, USA
LITERARY INDICATOR(S)- Meeting reports
PUBLISHER- AM INST PHYS
PUBLICATION
COUNTRY- WOODBURY, NY, (USA)
CONFERENCE DATE-
10/12-10/14/00
CONFERENCE TITLE- 2000 Annual Fall
Meeting of the Biomedical Engineering Society
CONFERENCE LOCATION- Washington, WA, USA
LANGUAGE- English
To activate the bFGF proliferative signal in myoblasts, the
cytoplasmic domain of FGF receptor-1 (FGFR-1) was fused to a modified FK506
binding domain (FKBP) and targeted to the plasma membrane. Mouse skeletal
myoblasts stably transfected with this construct were treated with a
bifunctional synthetic FKBP ligand (AP20187; ARIAD Pharmaceuticals) to
induce receptor dimerization. Results show that this genetically modified
receptor system can act as a dimerizer controlled growth switch and may
provide a means of specifically controlling transplanted myoblast expansion
in vivo.
DESCRIPTOR(S)- Cardiology; Cells;
Muscle;
Transplantation
(surgical)
IDENTIFIER(S)-
Heart
; Proliferation switch; Skeletal
myoblast
SECTIONAL CLASSIFICATION CODE- 461.1,
Biomedical Engineering; 461.2, Biological Materials; 461.6, Medicine;
462.4, Prosthetics .
33. Cardiac
systolic function before and after hematopoietic
stem
cell
transplantation
LSC 01-02
4749314 NDN-
122-0218-9599-4
Lehmann, S.; Isberg, B.; Ljungman, P.; Paul, C.
ABBREVIATED JOURNAL TITLE- Bone Marrow
Transplantation ÝBone Marrow Transplant.¨
vol. 26, no. 2,
pp. 187-192
20000702
DOCUMENT
TYPE- Journal Article
BIBLIOGRAPHIC LEVEL-
Analytical, Serial
ISSN- 0268-3369
AUTHOR AFFILIATION- Department of Hematology, Huddinge Sjukhus,
Karolinska Institute, 141 86 Huddinge, Sweden
LANGUAGE- English
In order to examine the effect of hematopoietic stem cell
transplantation (HSCT) on cardiac systolic function, we measured left
ventricular ejection fraction (LVEF) by radioventriculography (RVG) before
and after the transplantation procedure. One hundred and forty-eight
patients were examined, 96 undergoing allogeneic grafting and 52
autologous. Fifty patients had CML, 48 AML, 21 ALL, 18 multiple myeloma and
11 breast cancer. The second RVG examination was performed 22 to 227 days
(median 60 days) after HSCT. The mean LVEF value in the whole patient group
was 60.2% (range 39-81%) before and 61.1% (35-86%) after transplantation.
Patients with CML had significantly higher LVEF before transplantation than
patients with acute leukemia (P = 0.007) and multiple myeloma (P = 0.005).
No significant changes in mean LVEF between the pre- and post-transplant
measurements were seen in any of the diagnostic subgroups or in allogeneic
or autologous recipients. None of the 148 patients in the study has shown
any signs of clinical heart failure at 2, 5 to 10 years follow-up. Patients
who had received anthracyclines in the previous treatment had significantly
lower LVEF before transplantation but showed no increased risk of decline
in cardiac function. In conclusion, the HSCT procedure does not seem to
affect myocardial function 1-7 months after transplantation.
DESCRIPTOR(S)-
stem
cell
transplantation
; Blood pressure;
Heart
; Hemopoiesis
IDENTIFIER(S)- immunology; man
SECTIONAL
CLASSIFICATION CODE- 06833, Bone marrow .
34. High
treatment-related mortality in cardiac amyloid patients undergoing
autologous
stem
cell
transplant
LSC
99-11 4628054 NDN- 122-0202-9870-4
Saba, N.; Sutton, D. M.; Ross, H. J.; Siu, S.; Crump, R. M.;
Keating, A.; Stewart, A. K.*
ABBREVIATED JOURNAL TITLE- Bone Marrow
Transplantation ÝBone Marrow Transplant.¨
vol. 24, no. 8,
pp. 853-855
19991002
DOCUMENT
TYPE- Journal Article
BIBLIOGRAPHIC LEVEL-
Analytical, Serial
ISSN- 0268-3369
AUTHOR AFFILIATION- Princess Margaret Hospital, 610 University
Avenue, 5th floor - Room 126, Toronto, ON, M5G 2C4, Canada
LANGUAGE- English
Dose-intensive chemotherapy with PBSC support was recently reported
to be feasible in cardiac amyloidosis with some patients achieving
post-transplant improvement in performance status. At our center, 11
patients with symptomatic primary systemic amyloidosis and predominant
cardiac involvement confirmed by biopsy or increased wall thickness on
echocardiogram were evaluated for high-dose therapy. The average time from
diagnosis to referral was 11 months (4-26 months). Of the 11 patients, two
were not candidates for high-dose therapy, based on poor performance
status. The remaining nine patients proceeded to PBSC collection. Three
patients died during the mobilization period: two of rapid atrial
fibrillation, and the third secondary to progressive heart failure. Six
patients proceeded to transplantation. However, one died of sudden cardiac
arrest the day of melphalan administration, one following hypotension
related to stem cell infusion, and one of hypotensive shock the day
following stem cell infusion. Three patients recovered and left the
hospital, but one died of a cardiorespiratory event at home within 6 weeks
of discharge. Both surviving patients demonstrate objective improvement. A
decision to use high-dose therapy and stem cell support in cardiac
amyloidosis must balance the substantial morbidity of the procedure with
the potential benefits. Transplant regimens should avoid cardiotoxic agents
such as cyclophosphamide and DMSO and patients should receive
anti-arrythmic therapy.
DESCRIPTOR(S)-
stem
cell
transplantation
; Amyloidosis; Chemotherapy;
Heart
SECTIONAL CLASSIFICATION CODE- 06833, Bone marrow
.
35. Regenerating functional
myocardium
: Improved performance after
skeletal
myoblast
transplantation
LSC
98-12 4400079 NDN- 122-0190-7569-7
Taylor, D. A.; Atkins, B. Z.; Hungspreugs, P.; Jones, T. R.;
Reedy, M. C.; Hutcheson, K. A.; Glower, D. D.; Kraus, W. E.
ABBREVIATED JOURNAL TITLE- Nat.
Med.
vol. 4, no. 8, pp. 929-933
19980800
DOCUMENT TYPE- Journal Article
BIBLIOGRAPHIC LEVEL- Analytical, Serial
ISSN- 1078-8956
AUTHOR AFFILIATION-
Department of Medicine PO Box 3327, Duke University Medical Center, Durham,
NC 27710, USA
LANGUAGE- English
The adult heart lacks reserve cardiocytes and cannot regenerate.
Therefore, a large acute myocardial infarction often develops into
congestive heart failure. To attempt to prevent this progression, we
transplanted skeletal myoblasts into cryoinfarcted myocardium of the same
rabbits (autologous transfer), monitored cardiac function in vivo for two
to six weeks and examined serial sections of the hearts by light and
electron microscopy. Islands of different sizes comprising elongated,
striated cells that retained characteristics of both skeletal and cardiac
cells were found in the cryoinfarct. In rabbits in which myoblasts were
incorporated, myocardial performance was improved. The ability to
regenerate functioning muscle after autologous myoblast transplantation
could have a important effect on patients after acute myocardial
infarction.
DESCRIPTOR(S)-
Heart
; Muscles;
Myoblasts
; Myocardial infarction;
Myocardium
;
Transplantation
IDENTIFIER(S)- animal models;
rabbits
SECTIONAL CLASSIFICATION CODE- 33170,
Cellular based .
36. Induction
of stable chimerism and
transplantation
tolerance to rat islet and
heart
allografts by ultraviolet-B modulation of bone marrow cells.
LSC 93-09
2989079 NDN-
122-0122-8242-9
Jin, Ming-Xing; Engelstad, K.; Oluwole, S. F.
ABBREVIATED JOURNAL TITLE-
TRANSPLANTATION.
vol. 54, no. 1, pp. 113-118
1992
DOCUMENT TYPE- Journal Article
BIBLIOGRAPHIC LEVEL- Analytical, Serial
AUTHOR AFFILIATION- Dep. Surg., Coll. Physicians and Surg.
Columbia Univ., 630 W. 168th St., New York, NY 10032, USA
LANGUAGE- English
Ultraviolet-B irradiation (UV-B) (700 J/m super(2)) of BM cells
prior to transplantation into lethally gamma-irradiated (1050 rads)
allogeneic rats prevents the development of GVHD and results in stable
chimerism. This study was developed to determine if UV-B modulation of BMT
is useful for preconditioning recipients for the induction of tolerance to
donor islets and heart allografts. The results suggest that tolerance to
donor alloantigens in the UV-B BMT model is most likely due to selective
elimination of anti-BM donor helper or effector cell precursors (clonal
deletion) rather than induction of suppressor cell activity. This study
demonstrates that this relatively simple and effective approach to
modulation of T cells in BM treatment may be potentially useful in the
induction of tolerance to donor organs.
DESCRIPTOR(S)- allografts; bone
marrow;
heart
; immunological tolerance; islets of Langerhans; rats;
regulation;
stem
cells
; U. V. radiation
SECTIONAL
CLASSIFICATION CODE- 06828, Allograft .
37.
Stem
cell
transplantation
for repairment of injured
myocardium
MED 02-19
21928879 NDN-
222-0322-2078-9
Li, Q.; Gao, W.; Chen, G.
JOURNAL NAME- Zhonghua Yi Xue Za
Zhi
VOL. 81
NO. 22
2001 Nov 25
PP. 1401-3
26 reference(s)
DOCUMENT TYPE- Journal Article;
Review; Review, Tutorial
JOURNAL CODE-
7511141
JOURNAL SUBSET- MEDJSIM
ISSN- 0376-2491
PUBLICATION COUNTRY-
China
LANGUAGE- Chinese
NO-ABSTRACT
MEDICAL DESCRIPTOR(S)- *Bone Marrow
Cells --CY; *Graft vs Host Reaction --PH; *Hematopoietic
Stem
Cell
Transplantation
--TD; *Muscle, Skeletal --CY; *Myocardial Diseases
--TH Animal; Gene Therapy --MT; Hematopoietic
Stem
Cell
Transplantation
--MT; Human;
Stem
Cells
--CY;
Stem
Cells
--TR
MESH Z TREE NUMBER(S)- A11.148; A15.378.316;
G04.610.555.714.402; E04.936.225.350; A02.633.567; A10.690.350;
C14.280.600 .
38. Implantation of skeletal muscle
stem
cells
in inhibition of
fibroatrophy of ischemic
myocardium
: an experimental study
MED 02-19
21928868 NDN-
222-0322-2067-4
Wei, H.; Zhu, H.; Zhao, G.
JOURNAL NAME- Zhonghua Yi Xue Za
Zhi
VOL. 81
NO. 22
2001 Nov 25
PP. 1352-5
DOCUMENT TYPE- Journal Article
JOURNAL
CODE- 7511141
JOURNAL SUBSET- MEDJSIM
ISSN- 0376-2491
CORPORATE AUTHOR-
Department of Chest Surgerey, First Hospital Affiliated to Henan Medical
University, Zhengzhou 450052, China.
PUBLICATION
COUNTRY- China
LANGUAGE- Chinese
OBJECTIVE: To investigate the effect of stem cells derived from
autogenous skeletal muscle, namely satellite cells, and implanted into
ischemic myocardium on inhibition of myocardium fibroatrophy. METHODS: The
left anterodecendant arteries (LAD) of 12 adult dogs were ligated so as to
establish animal model of acute myocardiac infarction. Satellite cells
isolated from the greatest gluteal muscle of dogs were labeled with 4'
6-dimidino-2-phenylindone (DAPI), and then infused into the ventricular
myocardium of the isogenic dogs through LAD. Specimens of ischemic
myocardium were taken 2, 4, and 8 weeks after myoblast implantation.
Histologic sections are examined under common light microscope and
fluorescent microscope. Twelve dogs were used as controls. RESULTS: In the
ischemic myocardium where satellite cells had been implanted,
fibroaastrophy was efeectively inhibited. The implanted satellite cells had
differentiated into fully developed striated muscle cells. Vitreous
degeneration and disorder of basic structure could be observed in the
ischemic myocardium in the control group. CONCLUSION: The satellite cells
from autologous skeletal muscle differentiate into cardiac muscle cell-like
cells in the ischemic area and inhibit fibroatrophy of the ischemic
myocardium after implantation, thus bringing a hope of a new cure for
myocardial damage.
MEDICAL DESCRIPTOR(S)- *Cell
Differentiation --PH; *Myocardial Infarction --PA; *Myocardial Ischemia
--PA; *Perineuronal Satellite Cells --TR Animal; Disease
Models, Animal; Dogs; English Abstract; Hematopoietic
Stem
Cell
Transplantation
--MT; Hematopoietic
Stem
Cell
Transplantation
--TD; Muscle, Skeletal --CY; Myocardial Infarction --TH; Myocardial
Ischemia --TH;
Transplantation
, Autologous --MT
MESH
Z TREE NUMBER(S)- G04.335.151; G07.553.196; C14.280.647.500;
C14.907.553.470.500; C14.280.647; C14.907.553.470; A08.340.685;
A08.637.685; A11.650.685 .
39. Chimerism
of the
transplanted
heart
.
MED
02-19 21983156 NDN- 222-0321-6946-2
Bertolini, F.; Pruneri, G.
JOURNAL NAME- N Engl J Med
VOL. 346
NO. 18
2002 May 2
PP. 1410-2; discussion 1410-2
DOCUMENT TYPE- Comment; Letter
JOURNAL CODE- 0255562
JOURNAL SUBSET-
MEDJSAIM; MEDJSIM
ISSN- 1533-4406
COMMENTS IN- N Engl J Med. 2002 Jan 3;346(1):5-15
PUBLICATION COUNTRY- United States
LANGUAGE- English
NO-ABSTRACT
MEDICAL DESCRIPTOR(S)- *
Heart
Transplantation
; *
Myocardium
--CY; *
Transplantation
Chimera
Antigens, Ly --AN; Female; Hematopoietic
Stem
Cells
--CH;
Human; Male; Membrane Proteins --AN;
Myocardium
--CH; P-Glycoprotein
--AN;
Stem
Cell
Factor --AN;
Stem
Cells
--PH; Tissue
Donors
CAS SUBSTANCE NAME(S)- Antigens, Ly;
Membrane Proteins; P-Glycoprotein; Sca-1 antigen; Stem Cell Factor
MESH Z TREE NUMBER(S)- E04.100.376.475; E04.928.220.390;
E04.936.450.475; A02.633.580; A07.541.704; A10.690.637;
B01.030.530.750; B02.158.530.750 .
40. Preimplantation-stage
stem
cells
induce long-term allogeneic
graft acceptance without supplementary host conditioning.
MED 02-18
21679721 NDN-
222-0321-1882-0
Fandrich, F.; Lin, X.; Chai, G. X.; Schulze, M.; Ganten, D.;
Bader, M.; Holle, J.; Huang, D. S.; Parwaresch, R.; Zavazava, N.;
Binas, B.
JOURNAL NAME- Nat Med
2002 Feb
PP. 171-8
DOCUMENT
TYPE- Journal Article
JOURNAL CODE-
9502015
JOURNAL SUBSET- MEDJSIM
ISSN- 1078-8956
CORPORATE AUTHOR-
Department of General Surgery and Thoracic Surgery, University of Kiel,
24105 Kiel, Germany. ffaendrich@surgery.uni-kiel.de
COMMENTS IN- Nat Med. 2002 Feb;8(2):107-8
PUBLICATION COUNTRY- United States
LANGUAGE- English
Hematopoietic stem cells have been successfully employed for
tolerance induction in a variety of rodent and large animal studies.
However, clinical transplantation of fully allogeneic bone marrow or
blood-borne stem cells is still associated with major obstacles, such as
graft-versus-host disease or cytoreductive conditioning-related toxicity.
Here we show that when rat embryonic stem cell-like cells of WKY origin are
injected intraportally into fully MHC-mismatched DA rats, they engraft
permanently (>150 days) without supplementary host conditioning. This
deviation of a potentially alloreactive immune response sets the basis for
long-term graft acceptance of second-set transplanted WKY cardiac
allografts. Graft survival was strictly correlated with a state of mixed
chimerism, which required functional thymic host competence. Our results
provide a rationale for using preimplantation-stage stem cells as vehicles
in gene therapy and for the induction of long-term graft acceptance.
MEDICAL DESCRIPTOR(S)- *Fetal Tissue
Transplantation
; *Graft Survival --IM; *
Heart
Transplantation
--IM;
*Hematopoietic
Stem
Cell
Transplantation
; *Rats;
*
Transplantation
, Homologous --IM Animal; Blastocyst --CY;
Coculture; Graft vs Host Disease --PC; Lymphocyte Culture Test, Mixed;
Lymphocytes --CY; Lymphocytes --IM; Major Histocompatibility Complex;
Rats, Inbred ACI; Rats, Inbred WKY; Rats, Sprague-Dawley; Spleen --IM;
Support, Non-U.S. Gov't;
Transplantation
Chimera
MESH Z TREE NUMBER(S)- E04.936.580.300;
G04.610.555.714.545.340; E04.100.376.475; E04.928.220.390;
E04.936.450.475; E04.936.225.350; B02.649.865.635.560; E04.936.864
.
41. Evidence
for cardiomyocyte repopulation by extracardiac progenitors in
transplanted
human hearts.
MED
02-16 21932349 NDN- 222-0318-6533-1
Laflamme, M. A.; Myerson, D.; Saffitz, J. E.; Murry, C. E.
JOURNAL NAME- Circ Res
VOL. 90
2002 Apr 5
PP.
634-40
DOCUMENT TYPE- Journal Article
JOURNAL CODE- 0047103
JOURNAL SUBSET-
MEDJSIM
ISSN- 1524-4571
CORPORATE AUTHOR- Department of Pathology, University of
Washington, Seattle, Washington, USA.
CONTRACT/GRANT
NUMBER- CA-15074.CA.NCI; CA-18029.CA.NCI; PO1 HL03174.HL.NHLBI;
R24HL64387.HL.NHLBI; RO1 HL61553.HL.NHLBI
PUBLICATION
COUNTRY- United States
LANGUAGE- English
Human myocardium has long been considered to have essentially no
intrinsic regenerative capacity. Recent studies in rodent models, however,
have suggested the presence of an extracardiac stem cell population,
perhaps in bone marrow, that is capable of some reconstitution of
cardiomyocytes after injury. To determine whether similar mechanisms exist
in the human heart, we evaluated human female allograft hearts transplanted
into male patients. The presence of Y chromosomes in cardiomyocytes would
indicate these cells arose from the recipient, rather than the donor heart.
We identified 5 male patients who had retained a female heart at least 9
months before death and necropsy. Remarkably, in each case, the
transplanted heart contained a minute but readily detectable fraction of Y
chromosome-positive cardiomyocytes. The mean percentage of cardiomyocytes
arising from the host was estimated to be 0.04% with a median of 0.016%.
Most Y-positive cardiomyocytes were associated with regions of acute
rejection, suggesting such chimerism involves an injury event. Furthermore,
the sole patient whose immediate cause of death was allograft rejection
showed a much higher percentage of host-derived cardiomyocytes, up to 29%
in local, 1-mm(2) "hot spots." Thus, adult humans have extracardiac
progenitor cells capable of migrating to and repopulating damaged
myocardium, but this process occurs at very low levels.
MEDICAL DESCRIPTOR(S)- *
Heart
--PH;
*
Heart
Transplantation
; *Regeneration; *
Stem
Cells
--PH
Cell Differentiation; Cell Movement; Female; Human; Male;
Stem
Cells
--PA; Support, U.S. Gov't, P.H.S.;
Transplantation
Chimera;
Transplantation
, Homologous; Y Chromosome
MESH Z TREE NUMBER(S)- A07.541; E04.100.376.475;
E04.928.220.390; E04.936.450.475; G04.185.753; A11.872
.
42.
Transplantation
of embryonic
stem
cells
improves cardiac
function in postinfarcted rats.
MED
02-15 21611130 NDN- 222-0318-0089-0
Min, J. Y.; Yang, Y.; Converso, K. L.; Liu, L.; Huang, Q.;
Morgan, J. P.; Xiao, Y. F.
JOURNAL NAME- J Appl Physiol
VOL. 92
2002 Jan
PP. 288-96
DOCUMENT TYPE- Journal
Article
JOURNAL CODE- 8502536
JOURNAL SUBSET- MEDJSIM
ISSN-
8750-7587
CORPORATE AUTHOR- The Charles A. Dana
Research Institute and the Harvard-Thorndike Laboratory, Boston
Massachusetts 02215, USA.
PUBLICATION COUNTRY-
United States
LANGUAGE- English
Massive loss of cardiac myocytes after myocardial infarction (MI)
is a common cause of heart failure. The present study was designed to
investigate the improvement of cardiac function in MI rats after embryonic
stem (ES) cell transplantation. MI in rats was induced by ligation of the
left anterior descending coronary artery. Cultured ES cells used for cell
transplantation were transfected with the marker green fluorescent protein
(GFP). Animals in the treated group received intramyocardial injection of
ES cells in injured myocardium. Compared with the MI control group injected
with an equivalent volume of the cell-free medium, cardiac function in ES
cell-implanted MI animals was significantly improved 6 wk after cell
transplantation. The characteristic phenotype of engrafted ES cells was
identified in implanted myocardium by strong positive staining to
sarcomeric alpha-actin, cardiac alpha-myosin heavy chain, and troponin I.
GFP-positive cells in myocardium sectioned from MI hearts confirmed the
survival and differentiation of engrafted cells. In addition, single cells
isolated from cell-transplanted MI hearts showed rod-shaped GFP-positive
myocytes with typical striations. The present data demonstrate that ES cell
transplantation is a feasible and novel approach to improve ventricular
function in infarcted failing hearts.
MEDICAL DESCRIPTOR(S)- *Fetal Tissue
Transplantation
; *
Heart
--PP; *Myocardial Infarction --PP;
*Myocardial Infarction --TH; *
Stem
Cells
--TR Animal;
Cell Survival; Electrocardiography; Graft Survival; Hemodynamics --PH;
Immunohistochemistry; Isometric Contraction --PH; Male; Mice;
Myocardial Contraction --PH; Myocardial Infarction --PA;
Myocardium
--PA; Myosin Heavy Chains --ME; Rats; Rats, Wistar; Ventricular
Function, Left --PH
CAS SUBSTANCE NAME(S)- Myosin
Heavy Chains
MESH Z TREE NUMBER(S)-
E04.936.580.300; A07.541; C14.280.647.500; C14.907.553.470.500;
C14.280.647.500; C14.907.553.470.500; A11.872 .
43. Enhanced
myocyte-based biosensing of the blood-borne signals regulating
chronotropy.
MED 02-15
21655269 NDN-
222-0317-6747-3
Edelberg, J. M.; Jacobson, J. T.; Gidseg, D. S.; Tang, L.;
Christini, D. J.
JOURNAL NAME- J Appl Physiol
VOL. 92
2002 Feb
PP. 581-5
DOCUMENT TYPE- Journal
Article
JOURNAL CODE- 8502536
JOURNAL SUBSET- MEDJSIM
ISSN-
8750-7587
CORPORATE AUTHOR- Department of Medicine,
Weill Medical College, Cornell University, New York, New York 10021, USA.
jme2002@mail.med.cornell.edu
CONTRACT/GRANT NUMBER-
HL-59312.HL.NHLBI
PUBLICATION COUNTRY- United
States
LANGUAGE- English
Biosensors play a critical role in the real-time determination of
relevant functional physiological needs. However, typical in vivo
biosensors only approximate endogenous function via the measurement of
surrogate signals and, therefore, may often lack a high degree of dynamic
fidelity with physiological requirements. To overcome this limitation, we
have developed an excitable tissue-based implantable biosensor approach,
which exploits the inherent electropotential input-output relationship of
cardiac myocytes to measure the physiological regulatory inputs of
chronotropic demand via the detection of blood-borne signals. In this
study, we report the improvement of this application through the modulation
of host-biosensor communication via the enhancement of vascularization of
chronotropic complexes in mice. Moreover, in an effort to further improve
translational applicability as well as molecular plasticity, we have
advanced this approach by employing stem cell-derived cardiac myocyte
aggregates in place of whole cardiac tissue. Overall, these studies
demonstrate the potential of biologically based biosensors to predict
endogenous physiological dynamics and may facilitate the translation of
this approach for in vivo monitoring.
MEDICAL DESCRIPTOR(S)- *Biosensing
Techniques; *Blood Physiology; *Cell
Transplantation
; *
Heart
--PH;
*
Heart
Rate --PH; *
Heart
Transplantation
; *
Myocardium
--CY
Animal; Animals, Newborn; Cell Differentiation; Coronary
Circulation --PH; Embryo --CY; Kinetics; Mice; Neovascularization,
Physiologic --PH;
Stem
Cells
--CY; Support, Non-U.S. Gov't; Support,
U.S. Gov't, P.H.S.
MESH Z TREE NUMBER(S)-
E05.601.123; G09.188; E04.936.225; A07.541; G09.330.612.509;
E04.100.376.475; E04.928.220.390; E04.936.450.475; A02.633.580;
A07.541.704; A10.690.637 .
44. Human
mesenchymal
stem
cells
differentiate to a cardiomyocyte phenotype in
the adult murine
heart
.
MED
02-14 21634128 NDN- 222-0317-1298-8
Toma, C.; Pittenger, M. F.; Cahill, K. S.; Byrne, B. J.;
Kessler, P. D.
JOURNAL NAME- Circulation
VOL. 105
2002 Jan 1
PP.
93-8
DOCUMENT TYPE- Journal Article
JOURNAL CODE- 0147763
JOURNAL SUBSET-
MEDJSAIM; MEDJSIM
ISSN- 1524-4539
CORPORATE AUTHOR- Department of Medicine, Division of
Cardiology, Johns Hopkins School of Medicine, Baltimore, Md, USA.
PUBLICATION COUNTRY- United States
LANGUAGE- English
BACKGROUND: Cellular cardiomyoplasty has been proposed as an
alternative strategy for augmenting the function of diseased myocardium. We
investigated the potential of human mesenchymal stem cells (hMSCs) from
adult bone marrow to undergo myogenic differentiation once transplanted
into the adult murine myocardium. METHODS AND RESULTS: A small bone marrow
aspirate was taken from the iliac crest of healthy human volunteers, and
hMSCs were isolated as previously described. The stem cells, labeled with
lacZ, were injected into the left ventricle of CB17 SCID/beige adult mice.
At 4 days after injection, none of the engrafted hMSCs expressed myogenic
markers. A limited number of cells survived past 1 week and over time
morphologically resembled the surrounding host cardiomyocytes.
Immunohistochemistry revealed de novo expression of desmin, beta-myosin
heavy chain, alpha-actinin, cardiac troponin T, and phospholamban at levels
comparable to those of the host cardiomyocytes; sarcomeric organization of
the contractile proteins was observed. In comparison, neither cardiac
troponin T nor phospholamban was detected in the myotubes formed in vitro
by MyoD-transduced hMSCs. CONCLUSIONS: The purified hMSCs from adult bone
marrow engrafted in the myocardium appeared to differentiate into
cardiomyocytes. The persistence of the engrafted hMSCs and their in situ
differentiation in the heart may represent the basis for using these adult
stem cells for cellular cardiomyoplasty.
MEDICAL DESCRIPTOR(S)- *Cell
Differentiation; *Mesoderm --CY; *
Myocardium
--CY; *
Stem
Cells
--CY Adenoviridae --GE; Animal; Cell
Transplantation
;
Cytomegalovirus --GE; Genetic Vectors --GE; Human; Immunohistochemistry;
Lac Operon --GE; Mesoderm --ME; Mice;
Myocardium
--ME;
Stem
Cells
--ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.;
beta-Galactosidase --ME
CAS REGISTRY/EC NUMBER(S)-
*EC 3.2.1.23
CAS SUBSTANCE NAME(S)- Genetic
Vectors; beta-Galactosidase
MESH Z TREE NUMBER(S)-
G04.335.151; G07.553.196; A16.254.425.660; A02.633.580; A07.541.704;
A10.690.637; A11.872 .
45. Successful
non-myeloablative
stem
cell
transplantation
for a heavily transfused
woman with severe aplastic anemia complicated by
heart
failure.
MED 02-13
21640080 NDN-
222-0316-6035-6
Nishio, M.; Nakao, S.; Endo, T.; Fujimoto, K.; Takashima, H.;
Sakai, T.; Bacigalupo, A.; Koike, T.; Sawada, K.
JOURNAL NAME- Bone Marrow
Transplant
VOL. 28
2001 Oct
PP. 783-5
DOCUMENT TYPE- Journal
Article
JOURNAL CODE- 8702459
JOURNAL SUBSET- MEDJSIM
ISSN-
0268-3369
CORPORATE AUTHOR- Department of Internal
Medicine II, Hokkaido University, School of Medicine, Sapporo, Japan.
PUBLICATION COUNTRY- England
LANGUAGE- English
A 30-year-old Japanese woman weighing 35 kg with severe
hemochromatosis due to multiple transfusions was referred to our clinic for
treatment of severe aplastic anemia (SAA). The patient had heart failure
with an ejection fraction of 36% requiring diuretics and a severe liver
dysfunction with an indocyanine green clearance rate of 18%, as well as
other transfusion-related complications such as chronic hepatitis due to
hepatitis C virus and diabetes mellitus. She was treated with a
non-myeloablative preparative regimen that included fludarabine
monophosphate (Flu, 120 mg/m(2)), cyclophosphamide (CY, 1200 mg/m(2)) and
antithymocyte globulin (ATG, 15 mg/kg) followed by allogeneic peripheral
blood stem cell transplantation (PBSCT) from her HLA-matched sister. The
regimen was well tolerated, and engraftment rapidly occurred without any
therapy-related complications. Chimerism analysis on day 14 after
transplant showed reconstitution with 100% donor cells. She no longer
needed transfusion after day 23 and has been well in 90% Karnofsky status
at 4 months post transplant. The clinical course of this patient indicates
that this preparative regimen enables SAA patients with severe organ
failure to safely undergo allogeneic stem cell transplantation.
MEDICAL DESCRIPTOR(S)- *Anemia,
Aplastic --TH; *
Heart
Failure, Congestive --CO; *Hematopoietic
Stem
Cell
Transplantation
; *
Transplantation
Conditioning --MT
Adult; Anabolic Steroids --TU; Anemia, Aplastic --CO; Anemia,
Aplastic --DT; Antilymphocyte Serum --AD; Blood Transfusion --AE; Case
Report; Combined Modality Therapy; Cyclosporine --TU; Diabetes Mellitus
--CO; Female; Human; Immunosuppressive Agents --TU; Iron Overload --ET;
Methylprednisolone --TU; Support, Non-U.S. Gov't; T-Lymphocytes;
Transplantation
, Homologous; Vidarabine --AD; Vidarabine --AA
CAS REGISTRY/EC NUMBER(S)- *21679-14-1; *5536-17-4;
*59865-13-3; *83-43-2
CAS SUBSTANCE NAME(S)-
Anabolic Steroids; Antilymphocyte Serum; Immunosuppressive Agents;
fludarabine; Vidarabine; Cyclosporine; Methylprednisolone
MESH Z TREE NUMBER(S)- C15.378.071.085; C15.378.190.196;
C14.280.434; E04.936.225.350; E02.095.520.450.800; E05.478.610.800
.
46. Mechanical
circulatory support--a long and winding road.
MED 02-11
21824437 NDN-
222-0314-2372-3
McCarthy, P. M.; Smith, W. A.
JOURNAL NAME- Science
VOL. 295
NO. 5557
2002
Feb 8
PP. 998-9
17
reference(s)
DOCUMENT TYPE- Journal Article;
Review; Review, Tutorial
JOURNAL CODE-
0404511
JOURNAL SUBSET- MEDJSIM
ISSN- 1095-9203
CORPORATE AUTHOR-
Department of Thoracic and Cardiovascular Surgery, George M. and Linda H.
Kaufman Center for Heart Failure, Cleveland Clinic Foundation, Cleveland,
OH 44195, USA. mccartp@ccf.org
PUBLICATION COUNTRY-
United States
LANGUAGE- English
The highly public reintroduction of the total artificial heart last
year has prompted renewed interest in mechanical circulatory support
systems for the treatment of end-stage heart disease.
MEDICAL DESCRIPTOR(S)- *Cardiac
Output, Low --TH; *
Heart
Failure, Congestive --TH; *
Heart
,
Artificial; *Heart-Assist Devices Cardiac Output, Low --SU;
Cell
Transplantation
; Clinical Trials; Combined Modality Therapy;
Equipment Design;
Heart
Failure, Congestive --SU; Human;
Myocardium
--CY;
Stem
Cells
--TR
MESH Z TREE NUMBER(S)-
C14.280.148; C14.280.434; E07.695.300; E07.858.082.374; E04.050.430;
E07.695.300.300; E07.858.082.374.300 .
47. Serum
cardiac troponin I levels and ECG/Echo monitoring in breast cancer patients
undergoing high-dose (7 g/m(2)) cyclophosphamide.
MED 02-10
21426556 NDN-
222-0313-5831-7
Morandi, P.; Ruffini, P. A.; Benvenuto, G. M.; La Vecchia, L.;
Mezzena, G.; Raimondi, R.
JOURNAL NAME- Bone Marrow
Transplant
VOL. 28
2001 Aug
PP. 277-82
DOCUMENT TYPE-
Clinical Trial; Journal Article
JOURNAL CODE-
8702459
JOURNAL SUBSET- MEDJSIM
ISSN- 0268-3369
CORPORATE AUTHOR-
Division of Medical Oncology, San Bortolo Hospital, Vicenza, Italy.
PUBLICATION COUNTRY- England
LANGUAGE- English
High-dose cyclophosphamide (HD-CTX) is largely employed in
high-dose chemotherapy (HD-CHT) protocols. HD-CTX dose-limiting toxicity
expresses itself as cardiac toxicity which is fatal in a minority of
patients. The pathophysiology of HD-CTX-associated cardiotoxicity is still
poorly understood. Autopsy studies in patients who died from acute
HD-CTX-induced cardiac toxicity revealed hemorrhagic myocardial cell death
and interstitial edema. Recently troponins, in particular troponin I
(cTnI), have been found to represent a uniquely sensitive and specific
marker of myocyte membrane integrity and therefore to increase in response
to minimal myocardial cell damage in different settings, including
doxorubicin-induced cardiotoxicity. We performed a multiparametric
cardiologic monitoring in 16 consecutive breast cancer patients undergoing
HD-CTX by means of serial ECG registrations and cardiac enzymes (CPK,
CPK-MB and cTnI) determinations plus echocardiography in order to clarify
acute cardiac events following HD-CTX administration. Neither overt cardiac
toxicity nor cardiac enzymes elevation were recorded. Serial ECGs revealed
in six cases little and reversible reduction of QRS voltage and/or ST
abnormalities. Echo monitoring showed in four cases mild and transient
increase of LV diastolic/systolic diameter/volume without decrease of FS%
or EF% below normal values: in two of them abnormalities of diastolic
function (E/A mitral doppler ratio) were also recorded. We conclude that
our protocol of HD-CTX administration does not cause myocardial cell damage
as analyzed by serum cTnI levels, thus suggesting that myocyte membrane
injury may not be the first direct mechanism of HD-CTX cardiotoxicity. ECG
(ie QRS voltages ) and Echo (ie E/A ratio) monitoring leads us to
hypothesize that slight interstitial edema with reduction of LV diastolic
compliance may be initial signs of cardiac dysfunction in this clinical
setting.
MEDICAL DESCRIPTOR(S)- *Antineoplastic
Agents, Alkylating --TO; *Breast Neoplasms --DT; *Cyclophosphamide --TO;
*Electrocardiography --DE; *Troponin I --BL Adult;
Antineoplastic Agents, Alkylating --AD; Antineoplastic Combined
Chemotherapy Protocols --AD; Biological Markers --BL; Breast Neoplasms
--CO; Cyclophosphamide --AD; Dose-Response Relationship, Drug; Female;
Heart
Diseases --BL;
Heart
Diseases --CI;
Heart
Diseases --DI;
Hematopoietic
Stem
Cell
Transplantation
--AE; Human; Middle Age;
Transplantation
, Autologous --AE
CAS REGISTRY/EC
NUMBER(S)- *50-18-0
CAS SUBSTANCE NAME(S)-
Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy
Protocols; Biological Markers; Troponin I; Cyclophosphamide
MESH Z TREE NUMBER(S)- D05.569.035.035; D22.204.150;
D27.505.090.035; D27.505.130.204.150; C04.588.180; C19.146.170;
D02.455.526.728.650.730.243; D02.705.670.243; E01.370.370.380.240;
E01.370.405.240; D12.776.210.500.910.925; D12.776.220.525.825.925
.
48.
Stem
cell
research.
Stem
cells
may shore up
transplanted
hearts.
MED 02-06
21646900 NDN-
222-0309-4009-6
Seydel, C.
JOURNAL NAME- Science
VOL. 295
NO. 5553
2002
Jan 11
PP. 253-4
DOCUMENT
TYPE- News
JOURNAL CODE- 0404511
JOURNAL SUBSET- MEDJSIM
ISSN-
1095-9203
PUBLICATION COUNTRY- United States
LANGUAGE- English
NO-ABSTRACT
MEDICAL DESCRIPTOR(S)- *
Heart
Transplantation
; *
Myocardium
--CY; *
Stem
Cells
--PH;
*
Transplants
Cell Count; Cell Movement; Female;
Heart
--PH; Human; Male; Regeneration
MESH Z TREE
NUMBER(S)- E04.100.376.475; E04.928.220.390; E04.936.450.475;
A02.633.580; A07.541.704; A10.690.637; A11.872; E07.945
.
49. Effects of
dose-intensive chemotherapy and radiotherapy on serum n-terminal proatrial
natriuretic peptide in high-risk breast cancer patients.
MED 02-04
21445672 NDN-
222-0307-4237-7
Hall, K. S.; Wiklund, T.; Erikstein, B.; Holte, H.; Kvalheim,
G.; Sommer, H. H.; Andersen, A.; Skovlund, E.; Bergh, J.; Hall,
C.
JOURNAL NAME- Breast Cancer Res
Treat
VOL. 67
2001 Jun
PP. 235-44
DOCUMENT TYPE- Journal
Article
JOURNAL CODE- 8111104
JOURNAL SUBSET- MEDJSIM
ISSN-
0167-6806
CORPORATE AUTHOR- Department of Medical
Oncology and Radiotherapy, University of Oslo, Norway.
k.s.hall@klinmed.uio.no
PUBLICATION COUNTRY-
Netherlands
LANGUAGE- English
By using N-terminal proatrial natriuretic peptide (proANP) in serum
as a marker of cardiac function, we compared the cardiac side effects of
two intensive adjuvant treatment regimens for breast cancer. Patients
received either 9 cycles of FEC (5-fluorouracil, epirubicin and
cyclophosphamide) where the doses of epirubicin and cyclophosphamide were
escalated according to the leucocyte nadir (n = 49, FEC-group) or three
cycles of FEC followed by high-dose chemotherapy with alkylating agents (n
= 56, CTCb-group) given with the support of peripheral blood stem cells
support. Both groups received adjuvant radiotherapy. Serial measurements of
proANP were performed up to three years after treatment. Mean proANP values
in the FEC-group was on average 19% higher than in the CTCb-group (p =
0.002). The proANP levels showed a significant association with the
cumulative dose of epirubicin (p 60 0.001) but not with cyclophosphamide (p
= 0.151) and 5-FU (p = 0.160). The pharmacokinetics of epirubicin was
studied at the first and third chemotherapy course. The proANP levels after
treatment were significantly related to the AUC (p = 0.034) and Cmax(p =
0.037) of epirubicin. Left-sided chest irradiation was associated with on
average 12% higher proANP values than right-sided (p = 0.031). We conclude
that dose-escalated FEC causes a stronger increase in proANP than 3 FEC
followed by high-dose CTCb-treatment. Increase of proANP levels might
represent an early sign of cardiotoxicity secondary to chemotherapy and
radiation treatment. Long-time follow-up is necessary to determine the
clinical significance of these findings.
MEDICAL DESCRIPTOR(S)- *Antineoplastic
Combined Chemotherapy Protocols --AE; *Antineoplastic Combined
Chemotherapy Protocols --TU; *Atrial Natriuretic Factor --BL; *Biological
Markers --AN; *Breast Neoplasms --DT; *Breast Neoplasms --RT; *
Heart
--DE; *Protein Precursors --BL Adult; Antineoplastic
Combined Chemotherapy Protocols --AD; Breast Neoplasms --SU;
Chemotherapy, Adjuvant; Combined Modality Therapy; Cyclophosphamide --AD;
Dose-Response Relationship, Drug; Epirubicin --AD; Female; Fluorouracil
--AD; Hematopoietic
Stem
Cell
Transplantation
; Human; Middle Age;
Radiotherapy, Adjuvant; Risk Factors; Support, Non-U.S. Gov't
CAS REGISTRY/EC NUMBER(S)- *50-18-0; *51-21-8;
*56420-45-2; *85637-73-6
CAS SUBSTANCE NAME(S)-
Antineoplastic Combined Chemotherapy Protocols; Biological Markers; FEC
protocol; N-terminal proatrial natriuretic peptide; Protein Precursors;
Cyclophosphamide; Fluorouracil; Epirubicin; Atrial Natriuretic
Factor .
50.
Transplant
Center at Medical City Celebrates First 10 Years;
'The Nicolas Effect' Author Reg Green Is Special Guest.
NPA 02-04
81622469 NDN-
214-0463-1988-6
NO-AUTHOR
2002-01-11
PP.
DAF02111012002
DOCUMENT TYPE- PR Newswire
SOURCE OF ARTICLE(S)- Newswire
SPECIAL FEATURE(S)- COMPANY
LANGUAGE-
English, (DEF)
...Who:....The.Transplant.Center.@.Medical.City.Dallas
Hospital/North.Texas.Hospital.for.Children
What:...A.celebratory.gala.observing.the.10th.anniversary.of.the
transplant.program
When:...Saturday,.January.19,.2002,.6:00.-.10:00.PM
Where:..Hotel.Intercontinental,.Garden.Court,.15201.Dallas.Parkway,
Addison,.TX
Why:....Increase.organ.and.tissue.donation.awareness;.highlight.medical
advancements.in.organ.and.stem.cell.transplantation;.celebrate
the.lives.of.transplant.recipients.
PRE-EVENT.Press.Opportunities.(January.14th.-.18th):
--..By.appointment:..Interview.Patients.who.have.undergone.transplant
procedures.
--..See.Patient.Stories.Synopsis.(call.for.Fax/email.version)
--..Supporting.BetaSP.footage.available.request.(interviews,.b-roll)
--..Wednesday,.January.16th.4:00.PM.-.7:30.PM:..Pre-event.celebration.at
......the.hospital
--..Medical.City.Dallas.Hospital,.7777.Forest.Lane,.Atrium.D,.D
Conference.Center
--..Friday,.January.18th:..Interview.key-note.speaker,.Reg.Green
--..Angle:.Mr..Green.traveled.a.long.way.from.Switzerland.to.support.a
cause.that.is.near.and.dear.to.his.heart:.organ.and.tissue
donation...Mr..Green's.7-year.old.son,.Nicholas,.died.of.a.gunshot
wound.in.1994,.and.the.Green's.decision.to.donate.his.organs.not
only.saved.seven.other.lives,.it.led.to.a.national.movement.now
recalled.as.The.Nicholas.Effect.
--..Location:.Arriving.DFW,.Friday,.January.18th.at.2:15.PM.
British.Airways,.Flight..#2193...(To.arrange,.call.Silke.Jones
at.972.317.3858.or.214.912.7060)
--..Or.by.appointment.(Friday.2:00-.10:30.PM;.Saturday.by
appointment)
--..Supporting.BetaSP.footage.available.upon.request
EVENT.Press.Opportunities.(Saturday,.January.19th):
--..Interviews.by.appointment:
......--..Reg.Green,.Key.note.speaker
--..Britt.Berrett,.President.Medical.City.Dallas.Hospital.-.Master.of
Ceremonies
......--..Transplant.Program.Physicians/Staff
--..Patients.(BetaSP.interviews.and.supporting.b-roll.on.file.and
available.upon.request)
..--..Gala.Celebration.6:00.PM.-.10:00.PM
--..Patients.and.donor.families.in.attendance
To obtain Press
Release, Background Information and Patient Synopsis call Kristin at
1-888-972-3858.
CONTACT: Susan McBee, +1-972-566-7032, or Kristin
Rister, +1-972-317-3858, both for Medical City Dallas Hospital.
PRNewswire -- Jan. 11
COMPANY- Medical City Dallas
Hospital .
51. Cardiogene
and Intracardia Merge to Form Transatlantic Company to Develop Novel
Heart
Disease and Cell
Transplantation
Therapies.
NPA 00-46
66752300 NDN-
214-0426-0435-5
NO-AUTHOR
2000-11-09
PP.
NA
DOCUMENT TYPE- PR Newswire
SOURCE OF ARTICLE(S)- Newswire
LANGUAGE-
English, (DEF)
ERKRATH, Germany and CINCINNATI, Nov. 9 /PRNewswire/ --
Cardiogene AG and Intracardia, Inc. announced today that they havemerged to
create a transatlantic biopharmaceutical company pursuing multiple product
opportunities in
heart
disease and cell transplantation. In conjunction
with the merger, Cardiogene is changing its nameto Cardion AG to reflect
the broadening of its product portfolio andrepository of technology
platforms. The combined entity will retain corporate headquarters in
Erkrath, Germany and establish US operations in Boston, MA.
Cardion
combines Cardiogene's core local gene therapy platform with Intracardia's
strengths in
stem
cell
differentiation and graft enhancement. These two
synergistic assets will enable Cardion to advance a steady stream of
innovative products through clinical development, including:
--
NOStentin, a local nonviral gene therapy product for the prevention of
restenosis;
-- Cardioprotectin, a
stem
cell
based approach for
regeneration ofheart
tissue in the myocardial infarction setting.
"We are very excited about this transaction as Intracardia's
stem
cell
assets complement extremely well the existing products and
technologies under development in our company," stated Dr. Michael Ruhl,
CEO of the newly created Cardion. "Implementation of our business strategy
of creating a powerful product innovation platform from synergistic core
technologies has allowed us to evolve into a business with multiple product
opportunities addressing large unmet medical needs in some of the most
attractive pharmaceutical markets," added Dr. Ruhl.
The combined
company will possess non-viral local gene based products, developed by
Cardiogene, to reprogram damaged tissue "in situ" for the treatment of
cardiovascular disorders. Using a proprietary "plug and play" gene
delivery system comprising of a liposomal formulation and catheter
technology, therapeutic genes can be safely and efficiently delivered to
the blood vessel wall and
heart
tissue. The most advanced product,
NOStentin, is expected to enter into clinical trials before the end of
2000/early 2001 for the treatment of restenosis, the re-narrowing of an
artery previously dilated during angioplasty.
"We are very pleased
to have concluded the merger of Intracardia with Cardion. We have
carefully evaluated the fit of Dr. Loren Field's breakthrough technology
with the outstanding and evolving capabilities of Cardion, and see a
tremendous potential in the combined intellectual assets," Steve Gailar,
former President of Intracardia and Group Director, Venture Projects,
Sentron Medical commented. "We are highly confident in Cardion's
outstanding management team and scientists, and believe they will create
and implement a strategy that will leverage the combined technology
platform to yield products that will fill unmet clinical needs and create
significant shareholder value."
Intracardia contributes technology
pioneered by Dr. Loren Field ofthe Herman B. Wells Center for Pediatric
Research, Indianapolis. This technology allows the
differentiation/selection of
stem
cells
intoreplacement cells and is
expected to emerge as an important vehicle for ensuring safety in the
clinical application of
stem
cell
technology. In addition, Intracardia
provides multiple therapeutic genes forcardioprotection and control of
cardiomyocyte (cardiac cell) proliferation. The repository of assets
contributed by Intracardia combineswith Cardiogene's current development
products to provide a comprehensive offering for addressing many of the
most important manifestations of
heart
disease. One of these product
candidates, Cardioprotectin, is a
stem
cell
derived cardiomyocyte graft
for the treatment of myocardial infarction. Ex vivo differentiated
cardiomyocytes are grafted into the lesion site to promote the regeneration
of damaged contractile
heart
muscle and reconstitute left ventricular
function. The enabling
stem
cell
technology underlying Cardioprotectin
can be exploited to create regenerative grafts for many other diseases that
require reconstitution of damaged tissue/organs (e.g., pancreatic grafts
for the treatment of Type 1 diabetes).
"I am very pleased and
excited with the recent merger of Cardion and Intracardia. The level of
synergism between the collective intellectual properties is particularly
strong," commented Dr. Loren Field,Professor at the Herman B. Wells Center
for Pediatric Research. "Moreover, the network which is being developed
comprising Cardion in-house scientists, other corporate investigators and
collaborating academic investigators is truly outstanding, and will, in my
opinion, provide the best case scenario for the successful development of
allogenic
stem
cell
based therapies."
Cardion AG is a
transatlantic biopharmaceutical company integrating local non-viral gene
delivery and
stem
cell
technology to build a steady stream of
innovative
heart
disease and cell transplantation products. The Company
has a transatlantic presence with operating unitsbased in Erkrath, Germany
and Boston, USA.
EVENT DESCRIPTOR- #Acquisitions &
mergers, (150)
EVENT CODE(S)- 150
.
52.
Transplanted
Human
Stem
Cells
Develop Into Broad Range of
Tissues, Persist Over a Year in Research at The Children's Hospital of
Philadelphia.
NPA 00-45
66569473 NDN-
214-0424-5591-0
NO-AUTHOR
2000-10-30
PP.
6117
DOCUMENT TYPE- PR Newswire
SOURCE OF ARTICLE(S)- Newswire
SPECIAL
FEATURE(S)- COMPANY
LANGUAGE- English,
(DEF)
/ADVANCE FOR RELEASE AT 5 P.M. EST, TODAY/
/ADVANCE/
PHILADELPHIA, Oct. 30 /PRNewswire/ --
Adult human
stem
cells
taken from bone marrow have been induced todevelop into a wide range of
normal tissues, including bone, cartilage, fat, tendon and muscle, when
transplanted into fetal sheep. The transplanted human cells have persisted
in various sheep tissues for over one year without rejection by the sheep's
immune system. The study offers promise that in the future these cells may
be useful for tissue repair or regeneration and for treatment of
degenerative diseases such as muscular dystrophy.
"Although a great
deal of work remains to be done, these results suggest great potential for
the use of these cells in repair of damaged or degenerating tissues, or for
generation of new tissues, a process called tissue engineering," said Alan
W. Flake, M.D., director of The Children's Institute for Surgical Science
at The Children's Hospital of Philadelphia, who led the study reported in
the November issue of Nature Medicine. "One possible future application
might be the transplantation of normal
stem
cells
into a fetus
diagnosed with muscular dystrophy. "These cells could then act as a normal
stem
cell
`reservoir' and replace the abnormal muscle with normal
muscle as it degenerates over time."
Stem
cells
are immature
cells that develop into specialized cells throughout the body, and those
taken from embryos have the broadest potential for giving rise to all the
body's tissues. However, recent studies have shown that cells with broad
stem
cell
potential can be found in various adult tissues as well,
including the bone marrow and nervous system.
In the study at
Children's Hospital, researchers harvested mesenchymal
stem
cells
(MSCs) from adult bone marrow. "The transplanted cells developed in a
site-specific fashion," said Dr. Flake. "They migrated to different parts
of the sheep's body and differentiated into types of tissue present at each
site."
Because the transplanted cells carried human DNA, it was
possible to identify them in different tissue. They became cells in
skeletal muscle,
heart
muscle, bone, cartilage, the thymus gland and
stroma, which is supporting structure for bone marrow. Furthermore,
transplanted human MSCs were found at the site of clipped tails in the
sheep, suggesting that those cells were involved in wound healing.
MSC transplants may have a future role in enhancing wound healing after an
injury or surgery. Additionally, said Dr. Flake, because MSCs also develop
into supporting cells in bone marrow, they might provide a more favorable
environment for the transplanted cells used in bone marrow transplants for
leukemias and other blood-based diseases.MSCs might also be used in gene
therapy, acting as vehicles to deliver beneficial genes to targeted
tissues.
Although many institutions are currently investigating
various types of
stem
cells
, this is the first study examining
transplantation of human MSCs in the fetal sheep model. In this current
study, human MSCs were transplanted into fetal sheep early in gestation, at
either65 days or 85 days, before and after the brief window of time when
their immune systems mature and become active.
One surprise of the
study, according to Dr. Flake, is the persistence of these transplanted
cells even in animals that were capable of rejecting foreign cells at the
time of transplantation. "This suggests that these cells may have special
immunologic properties that may allow transplantation between individuals
or even between species without rejection or the need for toxic
immunosuppressive drugs," added Dr. Flake.
Collaborating with Dr.
Flake in the study was Kenneth W. Liechty, M.D., of Children's Hospital.
Other co-authors were from Children's Hospital and from Osiris Therapeutics
of Baltimore, Maryland, a biotechnology company.
Founded in 1855 as
the nation's first pediatric hospital, The Children's Hospital of
Philadelphia is recognized today as one of the leading treatment and
research facilities in the world. Through its long-standing commitment to
providing exceptional patient care, trainingnew generations of pediatric
healthcare professionals and pioneeringmajor research initiatives,
Children's Hospital has fostered discoveries that have benefited children
worldwide. Its pediatric research program is among the largest in the
country, ranking second in National Institutes of Health funding. In
addition, its unique outreach and public service programs have brought the
381-bed hospital recognition as a leading advocate for children from before
birth through age 19.
CONTACT: Maria Stearns of the Children's
Hospital of Philadelphia, 215-590-4091, or Stearnsm@email.chop.edu.
COMPANY- Children's Hospital
.
53. First Ever
Transplantation
of Skeletal Muscle Cells to Test Whether the Cells Can
Repair Damaged
Heart
Muscle.
NPA
00-40 65465445 NDN- 214-0420-0285-9
NO-AUTHOR
2000-09-25
PP.
6483
DOCUMENT TYPE- PR Newswire
SOURCE OF ARTICLE(S)- Newswire
SPECIAL
FEATURE(S)- INDUSTRY COMPANY
LANGUAGE- English,
(DEF)
PHILADELPHIA, Sept. 25 /PRNewswire/ --
To test whether it
will improve cardiac function, Temple University Hospital physicians have
transplanted a patient's own skeletal muscle cells (autologous
myoblasts
)
directly into a damaged area of his
heart
.
Because
heart
muscle
does not repair itself like skeletal muscle can, damage to the
heart
is
permanent. The hope is that the transplanted skeletal muscle cells will
help repair the damaged
heart
muscle and strengthen the patient's
heart
contractions.
There are two goals of this Phase I trial: (1) to
test the feasibility and safety of transplanting these cells into patients'
hearts and (2) to gain preliminary information on the cell's survival and
thepotential for improvement of cardiac function that might be associated
with the cell transplantation.
Dr. Howard Eisen, medical director of
Temple's
heart
transplantation program, and Dr. Satoshi Furukawa,
surgical director of Temple's
heart
transplantation program, are
co-principal investigators of the trial. The trial is run in collaboration
with and funded by Diacrin, Inc. (Nasdaq: DCRN).
A 48-year-old
Norristown, Pa., resident was the first patient to receive the transplanted
cells. After having a muscle biopsy taken from his arm, the biopsy was
transported to Diacrin's facility where the cells were isolated and
expanded in culture. Approximately two weeks later, the cells were
transplanted into the patient's
heart
duringsurgery to implant a left
ventricular assist device (LVAD). The patient is now on an LVAD waiting
for a
heart
transplant.
All patients enrolled in this FDA-approved
study will be candidates for
heart
transplantation and will be scheduled
for placement of anLVAD as a bridge to the transplantation. The cells are
transplantedinto the
heart
at the time of the surgery to implant the
LVAD.
Researchers will examine patients' hearts after transplant to
determine whether the skeletal cells survived and whether they helped
repair the damaged
heart
.
Coronary
heart
disease is the leading
cause of death in the UnitedStates, responsible for approximately one out
of every five deaths, or approximately 500,000 deaths each year. The
disease is caused by the accumulation of plaque on the walls of vessels
supplying blood tothe
heart
muscle. Rupture of unstable plaques promotes
clot formation that can block one or more of the coronary vessels resulting
in aninadequate supply of oxygen to the
heart
muscle. This highly
activemuscle is then quickly damaged and this damage cannot be repaired
with available therapies.
Temple University Hospital is a 486-bed
tertiary medical center located on Temple University's Health Sciences
Center campus in Philadelphia, Pa. Temple's
heart
failure program is one
of the largest in the country and recently celebrated the completion of its
800th
heart
transplant.
Diacrin, Inc., located in Charlestown,
Mass., is developing transplantable cells for the treatment of human
diseases which are characterized by cell dysfunction or cell death and for
which current therapies are either inadequate or nonexistent. Additional
products under development include: NeuroCell(TM)-PD for Parkinson's
disease; porcineneural cells for stroke, focal epilepsy and intractable
pain; porcine spinal cord cells for spinal cord injury; NeuroCell(TM)-HD
for Huntington's disease; porcine liver cells for acute liver failure;
human liver cells for cirrhosis; and porcine retinal pigment epithelial
cells for macular degeneration. Diacrin is developing NeuroCell(TM)-PD and
NeuroCell(TM)-HD in a joint venture with Genzyme Corporation.
GEOGRAPHIC DESCRIPTOR(S)- *United
States
PRODUCT DESCRIPTOR- #Drugs &
Pharmaceuticals, (2830000)
TICKER SYMBOL(S)-
DCRN
COUNTRY CODE(S)- 1USA
COMPANY- Diacrin Inc.
SECTION HEADING-
2830000, (Drugs & Pharmaceuticals) .
54. First Ever
Transplantation
of Skeletal Muscle Cells Into Patient's
Heart
to Test
Whether the Cells Can Repair Damaged
Heart
Muscle.
NPA 00-40
65467526 NDN-
214-0419-9568-3
NO-AUTHOR
2000-09-25
PP.
3008
DOCUMENT TYPE- Business Wire
SOURCE OF ARTICLE(S)- Newswire
SPECIAL
FEATURE(S)- INDUSTRY COMPANY
LANGUAGE- English,
(DEF)
Business/Technology Editors and Health/Medical Writers
PHILADELPHIA--(BW HealthWire)--Sept. 25, 2000
To test whether it
will improve cardiac function, Temple University Hospital physicians in
collaboration with Diacrin, Inc. (NASDAQ:DCRN) have transplanted a
patient's own skeletal muscle cells (autologous
myoblasts
) directly into
a damaged area of his
heart
.
Because
heart
muscle does not
repair itself like skeletal muscle can, damage to the
heart
is permanent.
The hope is that the transplanted skeletal muscle cells will help repair
the damaged
heart
muscle and strengthen the patient's
heart
contractions.
There are two goals of this Phase I trial: (1) to test
the feasibility and safety of transplanting these cells into patients'
hearts and (2) to gain preliminary information on the cell's survival and
the potential for improvement of cardiac function that might be associated
with the cell transplantation.
Dr. Howard Eisen, medical director of
Temple's
heart
transplantation program, and Dr. Satoshi Furukawa,
surgical director of Temple's
heart
transplantation program, are
co-principal investigators of this trial. The trial is run in collaboration
with and funded by Diacrin, Inc.
A 48-year-old Norristown, Pa.
resident was the first patient to receive the transplanted cells. After
having a muscle biopsy taken fromhis arm, the biopsy was transported to
Diacrin's facility where the cells were isolated and expanded in culture.
Approximately two weeks later, the cells were transplanted into the
patient's
heart
during surgery to implant a left ventricular assist
device (LVAD). The patientis now on an LVAD waiting for a
heart
transplant.
All patients enrolled in this FDA approved study will be
candidates for
heart
transplantation and will be scheduled for placement
of anLVAD as a bridge to the transplantation. The cells are transplanted
into the
heart
at the time of the surgery to implant the LVAD.
Researchers will examine patients' hearts after transplant to determine
whether the skeletal cells survived and whether they helped repair the
damaged
heart
.
Coronary
heart
disease is the leading cause of
death in the UnitedStates, responsible for approximately 1 of every 5
deaths, or approximately 500,000 deaths each year. The disease is caused by
the accumulation of plaque on the walls of vessels supplying blood to the
heartmuscle. Rupture of unstable plaques promotes clot formation that
canblock one or more of the coronary vessels resulting in an
inadequatesupply of oxygen to the
heart
muscle. This highly active muscle
is then quickly damaged and this damage can not be repaired with available
therapies.
Temple University Hospital is a 486-bed tertiary medical
center located on Temple University's Health Sciences Center campus in
Philadelphia, Pa. Temple's
heart
failure program is one of the largest in
the country and recently celebrated the completion of its 800th
heart
transplant.
Diacrin, Inc., located in Charlestown, Ma., is
developing transplantable cells for the treatment of human diseases which
are characterized by cell dysfunction or cell death and for which current
therapiesare either inadequate or nonexistent. Additional products under
development include: NeuroCell(TM)-PD for Parkinson's disease; porcine
neural cells for stroke, focal epilepsy and intractable pain; porcine
spinal cord cells for spinal cord injury; NeuroCell(TM)-HD for Huntington's
disease; porcine liver cells for acute liver failure; human liver cells for
cirrhosis; and porcine retinal pigment epithelial cells for macular
degeneration. Diacrin is developing NeuroCell(TM)-PD and NeuroCell(TM)-HD
in a joint venture with Genzyme Corporation.
PRODUCT DESCRIPTOR- #Drugs &
Pharmaceuticals, (2830000)
TICKER SYMBOL(S)-
DCRN
COMPANY- Diacrin Inc.
SECTION HEADING- 2830000, (Drugs & Pharmaceuticals)
.
55. Aastrom
Biosciences Awarded NIH Grant to Support Cord Blood
Transplant
Program.
NPA 00-31
63710685 NDN-
214-0413-3110-0
NO-AUTHOR
2000-07-27
PP.
9351
DOCUMENT TYPE- PR Newswire
SOURCE OF ARTICLE(S)- Newswire
SPECIAL
FEATURE(S)- INDUSTRY COMPANY
LANGUAGE- English,
(DEF)
- To Date, Company Has Received $1.8 Million in NIH Grant Awards
for
Advancements in Cord Blood
Stem
Cell
Therapy -
ANN
ARBOR, Mich., July 27 /PRNewswire/ --
Aastrom Biosciences, Inc.
(Nasdaq: ASTM) announced today that it was awarded a grant providing
funding of up to $829,000 over a two-year period. This grant will support
further development of the AastromReplicell(TM) System to produce umbilical
cord blood (UCB) derived cells used in
stem
cell
transplantation for
the treatment of leukemia and other blood diseases. The Phase II Small
Business Innovation and Research (SBIR) grant is from the National
Heart
Lung and Blood Institute of the National Institutes of Health (NIH).
Aastrom will collaborate with investigators at Duke University Medical
Center to performthis research.
"Aastrom has established the
state-of-the-art for ex vivo cord blood expansion," said R. Douglas
Armstrong, Ph.D., President and CEO ofAastrom. "This NIH award reflects the
continuing interest and clinical need for efficient, reliable and
cost-effective access to cord blood cells to treat patients who require a
stem
cell
transplant. Use of cord blood in the transplant setting has
demonstrated that clinicaloutcome appears to be linked to transplantation
cell dose. By increasing the number of available cells for transplant
using the AastromReplicell(TM) System, we hope to improve recoveries in
pediatric patients and to enable transplants to occur in adult patients
that might not otherwise be transplant candidates."
In December of
last year, the Company presented clinical results at the Annual Meeting of
the American Society of Hematology reporting that patients who received
cells produced with the AastromReplicell(TM) System showed an improvement
in the 100-day post transplant survival rates for the study patients when
compared to concurrent and historical control patients. In the April 2000
issue of Bone Marrow Transplantation, key clinical trial results were
published reporting successful engraftment of adult leukemia patients
treated with cells produced in the AastromReplicell(TM) System.
The
AastromReplicell(TM) System is a clinical system that consistsof an
instrumentation platform designed to operate a family of patient-specific
cell therapy kits for a broad range of cell therapy applications. Aastrom
plans to initiate a Phase III-type pivotal clinicalstudy of the CB-I
Therapy Kit for the production of cord blood cellsin the treatment of adult
leukemia patients. The objective of this study is to demonstrate the
capability of the AastromReplicell(TM) System to increase the
transplantation cell dose of an available cord blood sample to improve
patient recovery and to allow transplantation for patients that would
otherwise receive an inadequate cell dose.
The research to be
performed under this grant is an extension of the research previously
completed by the Company under a Phase I grantreceived last year. Through
this research, Aastrom found that the addition of stromal cells to serve as
"feeder cells" in cord blood expansions could significantly enhance overall
productivity, including the
stem
cell
component of the culture.
Research to be performed under the Phase II grant will also evaluate other
culture variables believed to affect overall cell culture performance.
These include the addition of growth factors, adjusting medium perfusion
rates and optimizing the concentration of the starting cell sample. The
Company hopes to show that an improved expansion process will lead to
greater clinical utility of cord blood in transplantation settings. The
grant will also support the development of Aastrom's CB-II Therapy Kit.
Pre-clinical research has shown the ability of this therapy kit to
significantly increase the number of key cells believed to provide
therapeuticvalue as compared to the CB-I Therapy Kit.
Umbilical cord
blood, which remains in the umbilical cord and the placenta after
childbirth, contains concentrations of
stem
cells
thatcan be used to
restore tissue destroyed by aggressive chemotherapy or radiation therapy
and represents a viable alternative to traditional
stem
cell
collection
procedures. This new technique may reduce theproblem of transplant
incompatibility, as donor tissue matching for transplants can be
comparatively easier for umbilical cord blood thanfor bone marrow-derived
stem
cells
. Due to the relatively small number of cells available from
a standard collection, cord blood
stem
cell
transplants have been used
primarily in smaller patients, and recovery times are often long. The
AastromReplicell(TM) System, an automated system that enables the
production of larger quantities of cellsfrom small starting samples, is
being evaluated to alleviate this cell dose limitation, increasing the
number of patients who may benefitfrom UCB transplantation. The growing
UCB banking infrastructure, together with the expansion capabilities of the
AastromReplicell(TM) System, should expand the use of cord blood
transplantation in patients with cancers, leukemias and other blood
diseases such as Wiskott-Aldrich Syndrome, Congenital Immunodeficiency
Syndrome and Fanconi's Anemia.
Aastrom Biosciences, Inc. is
pioneering the development of proprietary clinical systems including the
AastromReplicell(TM) System, a first of its kind product, to enable
physicians and patients greater accessibility to cells used for therapy.
The AastromReplicell(TM) System product line consists of an instrumentation
platform that can operate a growing number of patient-specific therapy kits
tailored to each cell therapy application. Aastrom has received patents
covering methods and devices for the ex vivo production of human stem and
other types of cells, as well as for the genetic modification of
stem
cells
. The AastromReplicell(TM) System is under development, and is not
available for sale at this time in the U.S., except for research and
investigational use.
This document contains forward-looking
statements, including without limitation, statements concerning intended
areas of research, product development objectives, clinical trial plans,
objectives and results, and potential advantages of the
AastromReplicell(TM) System, which involve certain risks and uncertainties.
The forward-looking statements are also identified through use of the words
"anticipates," "believes," "expects," "plans," "should" and other words of
similar meaning. Actual results may differ significantly from the
expectationscontained in the forward-looking statements. Among the factors
that may result in differences are the results obtained from research,
clinical trial and development activities, regulatory approval
requirements, the availability of resources and the degree to which the
Company's products achieve market acceptance. These and other significant
factors are discussed in greater detail in Aastrom's Annual Report
onForm-10K and other filings with the Securities and Exchange
Commission.
GEOGRAPHIC DESCRIPTOR(S)- *United
States
PRODUCT DESCRIPTOR- #Drugs &
Pharmaceuticals, (2830000)
TICKER SYMBOL(S)-
ASTM
COUNTRY CODE(S)- 1USA
COMPANY- Aastrom Biosciences Inc.
SECTION
HEADING- 2830000, (Drugs & Pharmaceuticals) .
56. Former Fred
Hutchinson Cancer Research Center Marrow
Transplant
Patients To Celebrate
Life at a Reunion in Seattle.
NPA
00-30 63570671 NDN- 214-0412-2877-5
NO-AUTHOR
2000-07-20
PP.
3128
DOCUMENT TYPE- PR Newswire
SOURCE OF ARTICLE(S)- Newswire
LANGUAGE-
English, (DEF)
The Legacy of the Hutchinson Center - More Than 500 Marrow
Transplant
Survivors to Converge on the Hutchinson Center One More
Time to Share Life
And Successes
SEATTLE, July 19
/PRNewswire/ --
Sharing memories, dreams and hopes for the future,
veterans of thebattle with cancer and other life-threatening diseases will
convergeon Seattle August 3-5, 2000, for Spirit of Seattle 2000, a former
patient reunion.
Celebrating life will be the highlight of this
three-day whirlwindaffair. Attendees include friends and family members of
hundreds of people who underwent a bone marrow or
stem
cell
transplant
at the Fred Hutchinson Cancer Research Center in the last 25 years.
As hosts of the patient reunion, the Hutchinson Center has planneda number
of activities including a celebration luncheon and dinner plus
presentations on the latest research findings and workshops on topics of
interest to the former patients and their families.
This is the
third former patient reunion hosted by the Center. The first reunion was
held in 1988 with the second following five yearslater in 1994. Patients
five or more years post transplant are invited to the Hutchinson Center.
The Spirit of Seattle Reunion is a prelude to the Fred Hutchinson
Cancer Research Center's 25th anniversary celebration beginning in
September. These veterans, and the many others, who have crossed the
Center's threshold in a search for a cure, bring meaning to the research
efforts at the Center. Their lives are a result of teamwork -- combining
knowledge, strength, courage and dedication on the part of the patient, the
families and Center staff.
"I was diagnosed with Aplastic Anemia in
1975. My primary oncologist refused to advise a trip to Seattle for an
experimental procedurecalled a bone marrow transplant, because he
considered it to be veryfoolish for my parents to bring me to Seattle
simply to die 1,200 miles away from home. However, there were also two
young residents assigned to my case, they had no plan to take no for an
answer. They lied about my physical condition to the Seattle doctors, and
arranged for an Air Force hospital place to fly me to Seattle. Once we
arrived in this strange, far away city, I was taken to the Public Health
Hospital on Beacon Hill to the seventh-floor, home of the miracle
workersthat were led by Don Thomas and his unbelievable staff. Their
prognosis was beyond grim ... they offered less than five percent chance
that I would survive. That was 29 years ago, and here I am, the second
longest survivor of a bone marrow transplant in the world. In the precious
words of Paul Harvey, 'now you know the rest of the story!'"
Steven
McCarty
Kent, Washington
August 1975
"I would like to
thank all the wonderful doctors, nurses and staffat the Fred Hutch for
caring and curing me while I was in the hospital."
Sharyn Kanada
Kaneohe, Hawaii
January 1984
"The nurses and doctors
were so wonderful that they inspired me tobecome a nurse. I became an R.N.
and have worked in the field of oncology, hospice and home health."
Jennifer Jo Caesar
Fiddletown, California
November 1977
"I work with the local cancer support group (Operation Uplift) to show
patients that survival and a great lifestyle are possible after cancer. I
also stress the importance of caregivers as my husband died in 1993 of lung
cancer so I have seen both sides of the cancer picture."
Mary Acker
Sequim, Washington
December 1988
"I feel very blessed
to be alive today, 23 years later. I will beforever thankful for Fred
Hutchinson, all the doctors and nurses, and, of course, Dr. Thomas.
Without them I would not be here today."
Ariel Shimondle
Seattle, Washington
August 1977
"I was told I had two years
to live with no options. Finding an answer was very difficult because all
the oncologists I talked with told me there was no hope. I was finally
told months later that one possibility was a bone marrow transplant and
Fred Hutchinson Cancer Research Center was the best place to go."
Jean Durko
Lake Zurich, IL
November 1984
"The Hutch
will always hold a special place in our hearts, especially the people."
Stanley Whitcomb
Carefree, Arizona
February 1991
"They referred me to the Fred Hutchinson Cancer Research Center inSeattle,
Washington, where I was cured and sent back home and am feeling very good.
The doctors, nurses and staff were wonderful people,very polite and very
caring."
Leroy Yost
Billings, Montana
March 1995
" ... part of my post-transplant experience is the gratitude I feel toward
the wonderful people who nurtured me through this journey --medical
personnel, family members, my donor, and friends. I was blessed and remain
blessed. The blessings began with a trusted family doctor who told me to
seek the best medical facility I could afford for this transplant ... the
best doctors available ... which led me to select Fred Hutchinson and its
medical staff."
Marla Murphy
Livonia, Michigan
November 1991
"After five years, Mom remains in remission. She has
faced medical difficulties in those years, but has met them all with an
incredible inner strength. She is very thankful for her care at the Hutch.
She believes that the kindness and care she received from the staff saved
her life. Our family is thankful to have her with us. She is anincredible
person and an inspiration."
Christine Calhoun about Cathleen Pape
Tenino, Washington
March 1995
"The Hutch Family, at
least that's what I felt like I was in, are truly amazing people. As you
walk in you can feel all the warmth around you; they are there to make your
stay a success. Without my support teams: my family, friends, church,
community and Hutch, I would not be here. Thanks to you all."
Patti
Binski-Walden
Cosmopolis, Washington
August 1986
"For
the past 14 years I have worked for home IV Infusion Company,enabling me to
use my insight and past experience to help others. In a nutshell, life is
good, but never easy!"
Claude Ritter
Oregon City, Oregon
July 1978
"I had been planning to be married before I became ill.
My fiancee came to Seattle the second week after my transplant. The day we
were told that the bone marrow test showed that my graft was showing
activity, Jim asked me 'again' to marry him ... We were married in my LAF
room ... We were able to spend the next 10 years celebrating thoselife
events that many take for granted. Jim passed away in 1994 from a
heart
problem, but we both were happy to have those years together thanks to the
gift of life from my sister and the Hutch."
Vicki Turnbull
Lexington, Kentucky
May 1984
"The Hutch's protocols were
considerably advanced, as compared to its competition. The patient support
staff is well managed and customer oriented. My nurse, Mary Hinds, was my
guardian angel. Knowing the Hutch's indisputable scientific achievements
this far, along with its innovative and collaborative approach, gives me
hope, and withouthope, life is not worth living."
Jill Bennett
Seattle, Washington
September 1994
"I feel I have and am
continuing to survive some incredible odds."
Teresa Anderson
Bremerton, Washington
January 1993
"On December 1, 1996 (my
second transplant, my first transplant was in 1986), I had a very
successful bone marrow transplant, had a perfect match from my sister. All
was wonderful for several years. I returned to Japan to teach. I became
pregnant. While undergoing pregnancy related medical tests, the doctors
found my leukemia had returned. I had my baby, a miracle, Matthew at 30
weeks. I had another bone marrow transplant in July 1996 and it was
another great success!"
Margaret Burns
Spokane, Washington
December 1986 and July 1996
"Since I was the oldest person to
ever have this procedure, my chance of survival was very low. There were
many ups and downs during the first year, but I was determined to beat the
odds. I'll never forget the eerie feeling of entering the cobalt room for
my first radiation treatment and hearing the large, heavy door slam shut
behind me.Memories also include being a part of the transplant team rather
than just a number. Thanks to that 'Fred Hutch' team, I'm now leading
anormal, active life."
Donald Prewitt
Lynnwood, Washington
November 1994
"I thank all of the staff that were there for
me and, most of all,I thank God for giving them the wisdom to treat those
who need it."
Irene Hook
Milton, Washington
November
1985
" ... my colleagues in Bethel School District to cover donor
search and recovery in Seattle, they were, and are, my angels on earth.
Myfirst grandchild was born three months after diagnosis. We are now
raising him, one friend says 'he's the reason I survived.' Linda Cassidy,
my donor, came from England to visit the U.S. for the first time in April
1998. My daughter, Megan, graduated from Seattle University in medical
technology. She now works for the University of Washington at Fred
Hutchinson Cancer Research Center on Lake Union. Full circle or what?"
JoAnn Trautman
Port Orchard, Washington
September 1994
"I had turned 27 years old when I was diagnosed with CML, and to say it was
scary is a huge understatement because I had only known oneother person who
had had it and he passed away within a very short period of time. All the
same I wanted to learn all I could about the disease and choose the best
course of action, but most of what you read is outdated in library books
and such which can be scary. However, through continued inquiry and advice
I was fortunate enough to havebeen led to FHCRC for a bone marrow
transplant. I stored my sperm in New York and Seattle. I am happy to say
that I am the proud fatherof Christopher John Roethel, Jr., and he, my
wife, Rosella, and I are all living a happy and healthy life."
Christopher Roethel
Hicksville, New York
...
NO-DESCRIPTORS .
57. Cord Blood
Registry - Sibling
Transplant
Success With Umbilical Cord Blood.
NPA 00-27
62888652 NDN-
214-0409-3108-9
NO-AUTHOR
2000-06-23
PP.
5772
DOCUMENT TYPE- PR Newswire
SOURCE OF ARTICLE(S)- Newswire
SPECIAL
FEATURE(S)- INDUSTRY COMPANY
LANGUAGE- English,
(DEF)
SAN BRUNO, Calif., June 23 /PRNewswire/ --
Families
freezing their newborn's cord blood for potential future use got a boost
today when researchers reported that cord blood transplants between matched
siblings were half as likely to result in the life-threatening complication
of graft vs. host disease than bone marrow transplants between matched
siblings. Graft vs. host disease, orGVHD, is a form of rejection that
kills up to 40% of transplant patients.
"Graft versus host disease
is the most important transplant-related complication," said Mary Horowitz,
M.D., professor of medicine at the Medical College and scientific director
of the International Bone Marrow Transplant Registry.
The study,
involving 2165 patients and appearing in the New England Journal of
Medicine, reported that although the incidence of GVHD was significantly
less with cord blood, the overall survival rate between the cord blood and
bone marrow groups was the same. "The reason survival was the same is that
there is a higher risk that the graft won't take since there are not as
many cells in the cord blood as in atypical bone marrow transplant. That
is the major problem with cordblood transplants," said Dr. Horowitz.
But that problem may be overcome as "cell expansion" techniques are
developed. Companies like Aastrom Biosciences have been active on Wall
Street lately with announcements of successful expansion of cordblood
stem
cells
, which were used to treat breast cancer patients. The
technology is based on an "incubator" approach, where a sample ofstem cells
is expanded into a larger number of cells which are then used in
transplant.
"As physicians continue to establish the transplant
potential of umbilical cord blood
stem
cells
, more parents are electing
to collect and save their newborn's cord blood for possible use in the
future," according to Stephen Grant, vice president of communications at
Cord Blood Registry, the country's largest cord blood bank. "In fact, a
number of our clients are physicians and scientists who know the current
uses and possible future applications of cord blood," Grant continued.
In the past 12 months, scientists have been opening new doors
intofuturistic applications of stem cells-cells which have the ability to
differentiate into other types of tissue and hold promise for the treatment
of a myriad of diseases.
In November, Japanese researchers reported
in a meeting of the American
Heart
Association, that they had isolated
certain types of cells found in umbilical cord blood, called "progenitor
endothelial cells," that may one day enable
heart
patients to "grow"
their own bypasses instead of having surgical vein grafts. The cells form
the lining of blood vessels and result in a process known as angiogenesis.
Cord Blood Registry is the nation's largest family cord blood bank.
Information regarding cord blood cell collection and banking is available
on the Internet at www.cordblood.com or through a toll-free number,
888-CORD-BLOOD or 888-267-3256.
PRODUCT DESCRIPTOR- #Medical Services
NEC, (8090000)
COMPANY- Cord Blood Registry
SECTION HEADING- 8090000, (Medical Services NEC)
.
58.
Stem
Cell
Transplantation
With Melphalan Effective For AL Amyloidosis
Treatment.
NWL 01-52
81015705 NDN-
102-0262-3395-1
NO-AUTHOR
JOURNAL NAME- Blood Weekly
2002-01-03
PP. 7
AVAILABILITY NOTE- THIS IS THE COMPLETE ARTICLE
SUPPLEMENTARY NOTE(S)- THIS IS THE FULL TEXT: COPYRIGHT 2002
NewsRX Subscription: $995.00 per year. Published weekly. P.O. Box 830409,
Birmingham, AL 35283-0409
PUBLISHER- NewsRX
SOURCE OF ARTICLE(S)- Newsletter
SPECIAL FEATURE(S)- LOB
ORIGINAL SERIAL
TITLE- 1065-6073
GEOGRAPHIC DESCRIPTOR(S)- *United
States
PRODUCT DESCRIPTOR- *Database Providers,
(7375000)
COUNTRY DESCRIPTOR- #United States, (3
30)
COUNTRY CODE(S)- 3 30
SECTION HEADING- 7375000, (Database Providers)
.
2001 DEC 27 - (NewsRx.com & NewsRx.net) -- by Michael Greer, senior
medical writer - Intensive chemotherapy combined with stem cell
transplantation can help patients suffering from AL amyloidosis,
researchers in the United States say "Primary or AL amyloidosis results
from a plasma cell dyscrasia in which fibrillar light chain protein
deposition leads to organ failure and death," explained Dr. Vaishali
Sanchorawala and colleagues at the Boston University School of Medicine in
Boston, Massachusetts.
While standard therapy for this
disorder offers little clinical benefit, high-dose melphalan-based
chemotherapy with stem cell transplantation (HDM/SCT) can produce
significant and persistent quality-of-life improvements, they said.
Sanchorawala and coworkers have treated over 200 AL amyloidosis
patients using the HDM/SCT treatment protocols that they developed. A
"substantial proportion" of these patients demonstrated lasting responses
to HDM/SCT therapy, with symptomatic and functional improvement and higher
survival rates, according to their report.
Patients can
tolerate this intensive therapy despite the organ dysfunction associated
with AL amyloidosis, the researchers found. However, HDM/SCT does carry a
significant toxicity risk, with a 14% peritransplant mortality rate.
The toxicity risk is especially pronounced for patients with
pre-existing heart dysfunction (An overview of the use of high-dose
melphalan with autologous stem cell transplantation for the treatment of AL
amyloidosis, Bone Marrow Transplantation, 2001;28(7):637-642).
"Based on our experience, we believe that HDM/SCT is the treatment of
choice for patients with AL amyloidosis who have a good performance status
and limited cardiac involvement at the time of diagnosis," Sanchorawala and
coauthors concluded. "HDM/SCT offers the best chance for hematologic
remission, prolongation of survival, and reversal of amyloid-related
disease."
The corresponding author for this report is Dr.
Vaishali Sanchorawala, Boston University Medical Center, 88 East Newton
Street, Boston, MA 02118, USA.
Key points reported in this
study include:
* High-dose melphalan chemotherapy with stem
cell transplantation (HDM/SCT) can benefit AL amyloidosis patients
* Many patients had lasting responses to HDM/SCT therapy, with
prolonged survival and improved quality of life
* By contrast,
standard treatments for AL amyloidosis offer little clinical benefit to
patients
* However, HDM/SCT does carry a substantial toxicity
risk, particularly for patients with cardiac dysfunction
This
article was prepared by Blood Weekly editors from staff and other reports.
59. Reprogrammed Human Cells Supply Tissue For
Transplantation
.
NWL 01-51
80783282 NDN-
102-0261-5414-5
NO-AUTHOR
JOURNAL NAME- Blood Weekly
2001-12-20
PP. 20
AVAILABILITY NOTE- THIS IS THE COMPLETE ARTICLE
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PUBLISHER- NewsRX
SOURCE OF ARTICLE(S)- Newsletter
SPECIAL FEATURE(S)- LOB COMPANY
ORIGINAL
SERIAL TITLE- 1065-6073
PRODUCT DESCRIPTOR- *Database
Providers, (7375000)
COMPANY- Advanced Cell
Technology Inc.
SECTION HEADING- 7375000,
(Database Providers) .
2001 DEC 20 - (NewsRx.com & NewsRx.net) -- Advanced Cell Technology,
Inc., (ACT) announced publication of its research on human somaticcell
nuclear transfer and parthenogenesis. The report provides the first proof
that reprogrammed human cells can supply tissue for transplantation Human
embryonic stem (ES) cells, and other cells derived from the inner cell mass
of the preimplantation embryo are totipotent, that is, they are capable of
forming any cell or tissue in the human body. While numerous human ES cell
lines are now in existence, they are of little value in human
transplantation, as they would be rejected by a patient as foreign. Human
therapeutic cloning has the potential to solve this problem by providing
cells that are an exact genetic match for the patient.
ACT's
paper, published in the Journal of Regenerative Medicine, reports
preliminary studies on two means of manufacturing such cells. The first
method is parthenogenesis. In this technique an egg cell is activated
without being fertilized by a sperm cell. A patient in need of a particular
cell or tissue type provides the egg cell, the activated egg cell forms a
preimplantation embryo, and the resulting stem cells are differentiated
into the type of tissue the patient needs.
The paper reports
success in activating egg cells in this manner to form many-celled embryos
resembling blastocysts. The paper does not report data on stem cell
isolation.
In a second series of studies, ACT performed
somatic cell nuclear transfer (cloning) to form preimplantation embryos. In
this instance, human egg cells were prepared by removing their DNA and
adding the DNA from a human somatic (body) cell. The paper reports that the
somatic nuclei showed evidence of reprogramming to an embryonic state as
evidenced by pronuclear development (a type of nucleus observed only in the
fertilized egg) and by early embryonic development to the six-cell stage.
Again, the company did not report on stem cell isolation.
"Our
preliminary results add to the weight of evidence that human cell
reprogramming is possible," said Jose B. Cibelli, PhD, DVM, ACT and the
first author of the report. "We understand that these are early and
preliminary results, but given the importance of this emerging field of
medicine we decided to publish our results now."
ACT's goal in
applying cloning to human medicine is to create stem cells capable of
differentiating into a variety of cells, such as heart cells, neurons,
blood cells, or islets for transplant therapies. "These are exciting
preliminary results," said Robert P. Lanza, MD, ACT and an author on the
paper. "This work sets the stage for human therapeutic cloning as a
potentially limitless source of immune-compatible cells for tissue
engineering and transplantation medicine. Our intention is not to create
cloned human beings, but rather to make lifesaving therapies for a wide
range of human disease conditions, including diabetes, strokes, cancer,
AIDS, and neurodegenerative disorders such as Parkinson and Alzheimer
disease."
"Human therapeutic cloning could be used for a host
of age-related diseases," said Michael D. West, PhD, ACT and an author of
the paper, "if the human cells behave as animal cells have in previous
studies, we may have found a means of rebuilding the lifespan of cells at
the same time. This would allow us to supply young cells of any kind,
identical to the patient, that could be used to address the tidal wave of
age-related disease that will accompany the aging of the population."
Researchers from Advanced Cell Technology collaborated with
scientists from Duncan Holly Biomedical of Somerville, Massachusetts on the
paper. The other authors are Kerrianne Cunniff of ACT, and Ann A. Kiessling
and Charlotte Richards.
This article was prepared by Blood
Weekly editors from staff and other reports.
60. Autologous
Stem
Cell
Transplantation
Can Reduce Damage.
NWL 01-43
79287234 NDN-
102-0256-5591-6
NO-AUTHOR
JOURNAL NAME- Blood Weekly
2001-11-01
PP. 18
AVAILABILITY NOTE- THIS IS THE COMPLETE ARTICLE
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PUBLISHER- NewsRX
SOURCE OF ARTICLE(S)- Newsletter
SPECIAL FEATURE(S)- LOB
ORIGINAL SERIAL
TITLE- 1065-6073
GEOGRAPHIC DESCRIPTOR(S)- *United
States
PRODUCT DESCRIPTOR- *Database Providers,
(7375000)
COUNTRY DESCRIPTOR- #United States,
(1USA)
COUNTRY CODE(S)- 1USA
SECTION HEADING- 7375000, (Database Providers)
.
2001 OCT 25 - (NewsRx.com & NewsRx.net) -- by Michael Greer, senior
medical writer - Researchers in Germany say that autologous stem cell
transplantation can be used to ameliorate cardiac damage after heart
attacks "The regenerative potential of human autologous adult stem cells on
myocardial regeneration and neovascularisation after myocardial infarction
may contribute to healing of the infarction area," according to B.E.
Strauer and colleagues at the University of Dusseldorf, Germany. "But no
clinical application has previously been reported."
Strauer
and coworkers described what they claim to be the first real-life
application of stem cells to regenerate heart tissue and improve
postinfarction cardiac function.
The researchers performed an
autologous bone marrow transplantation on a 46-year-old man 6 days after he
presented with a transmural infarction and left coronary artery occlusion.
They compared the ventricular function and tissue status, infarct size, and
blood flow before and after transplantation, according to their report.
Ten weeks after stem cell transplantation, the patient's
cardiac index had risen by up to 30%, as had his left ventricular ejection
fraction and stroke volume. Conversely, his end-diastolic volume and left
ventricular filling pressure during exercise had dropped by a similar
amount, study data showed.
Prior to transplantation, the
nfarct area was 24.6%. Ten weeks later, the infarct area had dropped to
15.7% ("Myocardial regeneration after intracoronary transplantation of
human autologous stem cells following acute myocardial infarction, Deutsche
Medizinische Wochenschrift, 2001;126(34-35):932-938).
"These
results for the first time demonstrate that selective intracoronary
transplantation of human autologous adult stem cells is possible under
clinical conditions and that it can lead to regeneration of the myocardial
scar after transmural infarction," Strauer and coauthors concluded. "The
therapeutic effects may be ascribed to stem cell-associated myocardial
regeneration and neovascularisation."
The corresponding author
for this report is B.E. Strauer, University of Dusseldorf, Klinik fur
Kardiologie, Pneumologie und Angiologie, Moorenstrasse 5, D-40225
Dusseldorf, Germany.
A search at www.NewsRx.net using the
terms "stem cell transplantation" and "bone marrow transplantation" yielded
150 articles in 26 specialized reports.
Key points reported in
this study include:
* Researchers have reported the first case
of autologous stem cells being used to help repair heart tissue after
myocardial infarction
* Bone marrow transplantation 6 days
after a heart attack resulted in a significant reduction in infarct area 10
weeks later
* Indices of heart function improved by roughly
30% after transplantation
This article was prepared by Blood
Weekly editors from staff and other reports.
61.
Transplants
Of Siblings' Cells Show Promise For Immune
Disorder.
NWL 01-14
72513048 NDN-
102-0244-4840-0
NO-AUTHOR
JOURNAL NAME- Blood Weekly
2001-04-05
PP. NA
AVAILABILITY NOTE- THIS IS THE COMPLETE ARTICLE
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Birmingham, AL 35283-0409
PUBLISHER- NewsRX
SOURCE OF ARTICLE(S)- Magazine/Journal
ORIGINAL SERIAL TITLE- 1065-6073
NO-DESCRIPTORS .
2001 APR 5 - (NewsRx.com & NewsRx.net) -- U.S. National Institutes of
Health (NIH) researchers in Bethesda, Maryland, have used a novel bone
marrow transplantation procedure to successfully transfer stem cells from
immunologically matched siblings into a small group of people who have a
rare, inherited immune disorder.
The disorder, chronic
granulomatous disease (CGD), leaves individuals vulnerable to
life-threatening infections and inflammatory growths, or granulomas, which
can damage the lungs, liver, and other organs.
Although it is
too soon to claim that the patients have been cured, the data so far
suggest that for patients in whom the transplant was successful, the immune
system is functioning significantly better than before treatment, the
investigators say.
"Non-myleloablative stem cell
transplantation has previously shown promise in leukemia and kidney cancer
patients," comments Anthony S. Fauci, MD, director of the National
Institute of Allergy and Infectious Diseases (NIAID), "but this is the
first clinical trial of this strategy in a series of patients who have an
inherited immune disorder."
The low-intensity stem cell
transplantation procedure, which uses no radiation, is less risky than
conventional stem cell transplantation because only some rather than all of
the patient's bone marrow cells are wiped out before the individual
receives the transplant. As a result, the transplanted patients have a
mixture of their own and their sibling's immune cells.
Results
of the CGD study, led by Mitchell E. Horwitz, MD, and Harry L. Malech, MD,
of NIAID's Laboratory of Host Defenses, appeared in the March 22, 2001,
issue of The New England Journal of Medicine.
CGD affects more
than 1,000 people in the United States and an estimated 25,000 people
worldwide. It is caused by several different gene mutations that prevent
white blood cells called neutrophils from making oxygen compounds that kill
bacteria and fungi. Based on studies of people with various types of the
mutation, the researchers project that restoring just 10% of neutrophils to
proper function may stave off recurrent CGD infections.
Recent
advances in treating CGD based on an immune-based therapy and antibiotics
have extended infection-free intervals and survival time in CGD patients.
But many people with the disorder still suffer recurrent bouts of
potentially deadly infections as well as a compromised quality of life.
Both the infections and the drugs taken to control them can damage vital
organs over time. In the United States, between 2% and 5% of those affected
by CGD die each year.
In the NEJM study, the NIAID group
attempted to move their efforts one giant step forward. "We wanted to
determine if there are ways to permanently restore proper immune cell
functioning without attempting to correct the underlying genetic defect,"
says Malech.
Horwitz notes, "We will not know whether this
treatment is a potential cure until we follow these patients for several
more years. But we are encouraged by the freedom from infection and
markedly improved quality of life that have come to the patients who have
been successfully transplanted."
Conventional stem cell
transplants require that the recipients' bone marrow be knocked out with
highly toxic drugs before the transplant procedure to reduce the chances
that the graft will be rejected. Because that early step carries a
significant risk of serious complications and death, such transplants are
most often considered a last-resort option for the sickest CGD patients.
To improve the odds of survival, Horwitz took the
non-myleloablative stem cell transplantation strategy that his colleague A.
John Barrett, MD, from the U.S. National Heart, Lung, and Blood Institute
(NHLBI), pioneered in kidney cancer and leukemia patients and tailored it
to CGD patients. Although conditioning regimens associated with
low-intensity stem cell transplants are less toxic that those of
conventional stem cell transplants, the risk of graft-versus-host disease
(GVHD) after the transplant is similar for the two procedures.
Donor T cells present in the stem cell graft are known to cause GVHD. To
rid the graft of T cells, Horwitz turned to the stem cell processing
expertise of Elizabeth J. Read, MD, and her colleagues in the NIH Clinical
Center Department of Transfusion Medicine. But T cells are necessary to
help fight infection and facilitate transplantation of the donor stem
cells. So Horwitz gradually began reintroducing donor T cells into the
patients beginning about one month after the transplant. Their goal in this
study was to achieve a stable presence of transplanted donor cells.
"In developing this strategy, we were walking a fine line between the
deleterious and beneficial effects of donor T cells," explains Horwitz.
"Without the re-infusion of donor T cells, 70% to 80% of the grafts would
be rejected," he says. "We had to gradually add back donor T cells over
time, enough to prevent rejection but not so much as to cause
graft-versus-host disease."
The study enrolled 10 people with
severe CGD between the ages of five and 36. Six of the study patients had
complete engraftment of donor stem cells, and another two had partial
engraftment. Overall, the transplant worked best in the five children who
were 12 years old or younger, only one of whom experienced a mild case of
GVHD. Three adults enrolled in the study died. One death was related to
GVHD, one was caused by an infection, and the third was due to
complications of a second transplantation after the first was
immunologically rejected.
In the median 18 months of
follow-up, the investigators have observed only one serious infection
characteristic of a patient with CGD disease. In addition, they have seen
resolution of pre-existing granulomas. Complete immune reconstitution after
stem cell transplantation, Horwitz notes, can take more than one year.
Despite fewer side effects, the new approach to stem cell
transplantation still carries considerable risks, the investigators
concede. In the future, they will fine-tune the procedure to further reduce
the risks. Horwitz is planning a new trial that will focus on younger
patients with severe CGD. They will be infused with fewer sibling T cells
in an attempt to achieve a permanent mixture of sibling and patient blood
cells, which data from the current trial indicate will increase the chances
of improving immune function and avoiding GVHD. This article was prepared
by Blood Weekly editors from staff and other reports. Copyright 2001, Blood
Weekly via NewsRx.com & NewsRx.net.
62. Merging
Companies to Develop
Heart
Disease and Cell
Transplantation
Therapies.
NWL 00-47
67049247 NDN-
102-0235-8156-5
NO-AUTHOR
JOURNAL NAME- Gene Therapy
Weekly
2000-11-23
PP. NA
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2000 Charles W. Henderson Subscription: $1368.00 per year. Published
weekly. P.O. Box 830409, Birmingham, AL 35283-0409.
PUBLISHER- Charles W. Henderson
SOURCE OF
ARTICLE(S)- Newsletter
SPECIAL FEATURE(S)-
COMPANY
ORIGINAL SERIAL TITLE- 1078-2842
COMPANY- Intracardia Inc.
.
2000 NOV 23 - (NewsRx.com) -- Cardiogene AG, Erkrath, Germany, and
Intracardia, Inc., Cincinnati, Ohio, announced that they have merged to
create a transatlantic biopharmaceutical company pursuing multiple product
opportunities in heart disease and cell transplantation.
In
conjunction with the merger, Cardiogene is changing its name to Cardion AG
to reflect the broadening of its product portfolio and repository of
technology platforms. The combined entity will retain corporate
headquarters in Erkrath, Germany, and establish U.S. operations in Boston,
Massachusetts.
Cardion combines Cardiogene's core local gene
therapy platform with Intracardia's strengths in stem cell differentiation
and graft enhancement. These two synergistic assets will enable Cardion to
advance a steady stream of innovative products through clinical
development, including NOStentin, a local non-viral gene therapy product
for the prevention of restenosis; and Cardioprotectin, a stem-cell-based
approach for regeneration of heart tissue in the myocardial infarction
setting.
The combined company will possess non-viral local
gene-based products, developed by Cardiogene, to reprogram damaged tissue
in situ for the treatment of cardiovascular disorders. Using a proprietary
"plug and play" gene delivery system comprising a liposomal formulation and
catheter technology, therapeutic genes can be safely and efficiently
delivered to the blood vessel wall and heart tissue. The most advanced
product, NOStentin, is expected to enter into clinical trials before the
end of 2000/early 2001 for the treatment of restenosis, the re-narrowing of
an artery previously dilated during angioplasty.
Intracardia
contributes technology pioneered by Dr. Loren Field of the Herman B. Wells
Center for Pediatric Research, Indianapolis, Indiana. This technology
allows the differentiation/selection of stem cells into replacement cells
and is expected to emerge as an important vehicle for ensuring safety in
the clinical application of stem cell technology.
In addition,
Intracardia provides multiple therapeutic genes for cardioprotection and
control of cardiomyocyte proliferation. The repository of assets
contributed by Intracardia combines with Cardiogene's current development
products to provide a comprehensive offering for addressing many of the
most important manifestations of heart disease. One of these product
candidates, Cardioprotectin, is a stem cell derived cardiomyocyte graft for
the treatment of myocardial infarction.
Ex vivo differentiated
cardiomyocytes are grafted into the lesion site to promote the regeneration
of damaged contractile heart muscle and reconstitute left ventricular
function. The enabling stem cell technology underlying Cardioprotectin can
be exploited to create regenerative grafts for many other diseases that
require reconstitution of damaged tissue/organs (e.g., pancreatic grafts
for the treatment of type 1 diabetes).
This article was
prepared by Gene Therapy Weekly editors from staff and other reports.
Copyright 2000, Gene Therapy Weekly via NewsRx.com.
63. Human
Stem
Cells
Transplanted
into Sheep Develop into Broad Range of
Tissues.
NWL 00-46
66807837 NDN-
102-0235-7701-0
NO-AUTHOR
JOURNAL NAME- Blood Weekly
2000-11-16
PP. NA
AVAILABILITY NOTE- THIS IS THE COMPLETE ARTICLE
SUPPLEMENTARY NOTE(S)- THIS IS THE FULL TEXT: COPYRIGHT 2000
Charles W. Henderson Subscription: $995.00 per year. Published weekly. P.O.
Box 830409, Birmingham, AL 35283-0409.
PUBLISHER-
Charles W. Henderson
SOURCE OF ARTICLE(S)-
Magazine/Journal
ORIGINAL SERIAL TITLE-
1065-6073
NO-DESCRIPTORS .
2000 NOV 16 - (NewsRx.com) -- Adult human stem cells taken from bone
marrow have been induced to develop into a wide range of normal tissues,
including bone, cartilage, fat, tendon, and muscle, when transplanted into
fetal sheep.
The transplanted human cells have persisted in
various sheep tissues for over one year without rejection by the sheep's
immune system. The study offers promise that in the future these cells may
be useful for tissue repair or regeneration and for treatment of
degenerative diseases such as muscular dystrophy.
"Although a
great deal of work remains to be done, these results suggest great
potential for the use of these cells in repair of damaged or degenerating
tissues, or for generation of new tissues, a process called tissue
engineering," said Alan W. Flake, MD, The Children's Institute for Surgical
Science at The Children's Hospital of Philadelphia, Pennsylvania, who led
the study reported in the November 2000 issue of Nature Medicine.
"One possible future application might be the transplantation of
normal stem cells into a fetus diagnosed with muscular dystrophy. These
cells could then act as a normal stem cell 'reservoir' and replace the
abnormal muscle with normal muscle as it degenerates over time," Flake
continued.
Stem cells are immature cells that develop into
specialized cells throughout the body, and those taken from embryos have
the broadest potential for giving rise to all the body's tissues. However,
recent studies have shown that cells with broad stem cell potential can be
found in various adult tissues as well, including the bone marrow and
nervous system.
In the study at Children's Hospital,
researchers harvested mesenchymal stem cells (MSCs) from adult bone marrow.
"The transplanted cells developed in a site-specific fashion," said Flake.
"They migrated to different parts of the sheep's body and differentiated
into types of tissue present at each site."
Because the
transplanted cells carried human DNA, it was possible to identify them in
different tissue. They became cells in skeletal muscle, heart muscle, bone,
cartilage, the thymus gland, and stroma, which is supporting structure for
bone marrow. Furthermore, transplanted human MSCs were found at the site of
clipped tails in the sheep, suggesting that those cells were involved in
wound healing.
MSC transplants may have a future role in
enhancing wound healing after an injury or surgery. Additionally, said
Flake, because MSCs also develop into supporting cells in bone marrow, they
might provide a more favorable environment for the transplanted cells used
in bone marrow transplants for leukemias and other blood-based diseases.
MSCs might also be used in gene therapy, acting as vehicles to deliver
beneficial genes to targeted tissues.
Although many
institutions are currently investigating various types of stem cells, this
is the first study examining transplantation of human MSCs in the fetal
sheep model. In this current study, human MSCs were transplanted into fetal
sheep early in gestation, at either 65 days or 85 days, before and after
the brief window of time when their immune systems mature and become
active.
One surprise of the study, according to Flake, is the
persistence of these transplanted cells even in animals that were capable
of rejecting foreign cells at the time of transplantation. "This suggests
that these cells may have special immunologic properties that may allow
transplantation between individuals or even between speci