Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells

Myocyte loss in the ischemically injured mammalian heart often leads to irr eversible deficits in cardiac function. To identify a source of stem cells capable of restoring damaged cardiac tissue, we transplanted highly enriche d hematopoietic stem cells, the so-called side population (SP) cells, into lethally irradiated mice subsequently rendered ischemic by coronary artery occlusion for 60 minutes followed by reperfusion. The engrafted SP cells (C D34(-)/low, c-Kit(+), Sca-1(+)) or their progeny migrated into ischemic car diac muscle and blood vessels, differentiated to cardiomyocytes and endothe lial cells, and contributed to the formation of functional tissue. SP cells were purified from Rosa26 transgenic mice, which express 1acZ widely. Dono r-derived cardiomyocytes were found primarily in the peri-infarct region at a prevalence of around 0.02% and were identified by expression of lacZ and alpha -actinin, and lack of expression of CD45. Donor-derived endothelial cells were identified by expression of lacZ and Flt-1, an endothelial marke r shown to be absent on SP cells. Endothelial engraftment was found at a pr evalence of around 3.3%, primarily in small vessels adjacent to the infarct . Our results demonstrate the cardiomyogenic potential of hematopoietic ste m cells and suggest a therapeutic strategy that eventually could benefit pa tients with myocardial infarction.