Copyright © 2006, European Society of Cardiology
Intramyocardial delivery of human CD133+ cells in a SCID mouse cryoinjury model: Bone marrow vs. cord blood-derived cells
aDepartment of Cardiac Surgery, University of Rostock, Rostock, Germany
bMiltenyi Biotec GmbH, Research and Development, Germany
cVita34, Leipzig, Germany
* Corresponding author. Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Tel.: +49 30 4591 2109; fax: +49 30 862 3071. Email address: stamm{at}dhzb.de
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 105 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. Scar 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.
KEYWORDS Cell therapy; Angiogenesis; Cell differentiation; Stem cells
1 Both authors equally contributed to this article.
2 Current address: German Heart Institute Berlin, Cardiac Surgery, Augustenburger Platz 1, 13353 Berlin, Germany.
Time for primary review 25 days
This work was supported in part by the German Minister of Research (BMBF FKZ 01ZZ0108 and FKZ 01GN0536) and the Minister of Economy of Saxony (SAB 7522/1193).
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