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 (BMCD133) or cord blood (UCBCD133) 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. Sear size, capillary density, and cardiomyocyte apoptosis were evaluated by histology. In addition, the myogenic, and endothelial differentiation capacity of BMCD133 and UCBCD133 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 BMCD133 and UCBCD133 cell-treated CI+ mice was higher than in control CI+ mice, but not different between BMCD133 and UCBCD133 cell-treated hearts. There were no differences in scar size and myocardial mass among BMCD133, UCBCD133 and control CI+ mice, but cardiomyocyte apoptosis was reduced by both BMCD133 and UCBCD133 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 BMCD133 cells (45.4 +/- 0.9%), but not by UCBCD133 cells (40.8 +/- 0.7%). On the other hand, both BMCD133 and UCBCD133 cells abolished post-injury mortality. In vitro, neither cultivated BMCD133 or UCBCD133 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. (c) 2006 European Society of Cardiology. Published by Elsevier B.V.