Differentiation and migration of Sca1+/CD31-cardiac side population cells in a murine myocardial ischemic model

Background: Side population cells are a rare subset of cells found in the adult heart that are highly enriched for stem and progenitor cell activity. Recent studies have suggested that Sca1+/CD31- cardiac side population cells are capable of differentiation into cardiomyocytes in vitro. However, the response of these cells to myocardial injury remains unknown in vivo. Methods: Sca1+/CD31- cardiac side population cells were isolated from mouse (C57BL6/J) hearts by FACS. These cells were labeled and delivered via an intramyocardial injection into an infracted mouse heart. The differentiation potential of these cells was determined by immunohistochemistry two weeks later. We further tested the migration potential and the relationship of SDF-1 alpha/CXCR4 to these cells. Results: The transplanted cells were found to express cardiomyocyte or endothelial cell specific markers. Furthermore, when these cells were transplanted into non-infarct myocardium after myocardial infarction, they were found in the damaged myocardium. Consistent with their homing property, we found that SDF-1 alpha and CXCR4 were up-regulated in the damaged myocardium and on Sca1+/CD31- cardiac side population cells respectively following myocardial infarction. We also show that SDF-1 alpha induced migration of Sca1+/CD31- cardiac side population cells in vitro. Conclusions: Our results have suggested that Sca1+/CD31- cardiac side population cells are able to migrate into damaged myocardium from non-ischemic area of the heart and differentiate into both cardiomyocyte- and endothelial-like cells following acute ischemic injury. The SDF-1 alpha/CXCR4 system might play an important role in the migration of these cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.