Intramyocardial delivery of human CD133+ cells in a SCID mouse cryoinjury model: Bone marrow vs. cord blood-derived cells.
OBJECTIVE
The regenerative potential of endothelial and hematopoietic progenitor cells in the heart may vary according to their origin. This study was designed to compare the functional effects of CD133+ cells from human cord blood and bone marrow in a mouse model of myocardial injury.


METHODS
5 x 10(5) CD133+ cells from bone marrow (BM(CD133)) or cord blood (UCB(CD133)) were injected in the necrosis border zone of NOD/SCID (non-obese diabetic/severe combined immunodeficiency) mice with left ventricular cryoinjury (CI+). Transplanted cells were tracked by immunostaining for hNuclear antigen and by PCR for hDNA. Echocardiography was used to measure contractility. Scar size, capillary density, and cardiomyocyte apoptosis were evaluated by histology. In addition, the myogenic and endothelial differentiation capacity of BM(CD133) and UCB(CD133) was compared in vitro.


RESULTS
DNA was detected 4 weeks after cell injection by PCR, but hNuc+ cells were found by immunostaining only after 48 h. Capillary density in both BM(CD133) and UCB(CD133) cell-treated CI+ mice was higher than in control CI+ mice, but not different between BM(CD133) and UCB(CD133) cell-treated hearts. There were no differences in scar size and myocardial mass among BM(CD133), UCB(CD133) and control CI+ mice, but cardiomyocyte apoptosis was reduced by both BM(CD133) and UCB(CD133) cells. The post-injury deterioration of shortening fraction (46.2+/-1% in sham-operated mice and 41.3+/-0.8% in control CI+ mice) was prevented by BM(CD133) cells (45.4+/-0.9%), but not by UCB(CD133) cells (40.8+/-0.7%). On the other hand, both BM(CD133) and UCB(CD133) cells abolished post-injury mortality. In vitro, neither cultivated BM(CD133) or UCB(CD133) cells developed into myocytes, but both readily differentiated towards an endothelial cell phenotype.


CONCLUSIONS
While both cord blood and marrow CD133+ cells have some beneficial effects on post-injury angiogenesis and survival, only marrow cells appear to improve myocardial contractility.
Ma
Nan
N
Department of Cardiac Surgery, University of Rostock, Rostock, Germany.
Ladilov
Yury
Y
Moebius
Jeannette M
JM
Ong
Leelee
L
Piechaczek
Christoph
C
Dávid
Arpád
A
Kaminski
Alexander
A
Choi
Yeong-Hoon
YH
Li
Wenzhong
W
Egger
Dietmar
D
Stamm
Christof
C
Steinhoff
Gustav
G
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis; D016026:Bone Marrow Transplantation / Q000379:methods*; D002196:Capillaries; D009202:Cardiomyopathies / Q000276:immunology / Q000503:physiopathology / Q000601:surgery*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003080:Cold Temperature / Q000009:adverse effects; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D004452:Echocardiography; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007267:Injections; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology; D009336:Necrosis; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000276:immunology; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse