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

TLDR

Myocyte loss in the ischemically injured mammalian heart often leads to irreversible deficits in cardiac function. The study aimed to identify stem cells capable of restoring damaged cardiac tissue by transplanting side‑population hematopoietic stem cells into irradiated mice that underwent 60‑minute coronary occlusion and reperfusion. SP cells were isolated from Rosa26 transgenic mice expressing lacZ and transplanted into these irradiated, ischemic mice. Engrafted SP cells differentiated into cardiomyocytes and endothelial cells, with donor‑derived cardiomyocytes at ~0.02% in the peri‑infarct region and endothelial cells at ~3.3% in small vessels, demonstrating the cardiomyogenic potential of hematopoietic stem cells and suggesting a therapeutic strategy for myocardial infarction.

Abstract

Myocyte loss in the ischemically injured mammalian heart often leads to irreversible deficits in cardiac function. To identify a source of stem cells capable of restoring damaged cardiac tissue, we transplanted highly enriched 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 (CD34–/low, c-Kit+, Sca-1+) or their progeny migrated into ischemic cardiac muscle and blood vessels, differentiated to cardiomyocytes and endothelial cells, and contributed to the formation of functional tissue. SP cells were purified from Rosa26 transgenic mice, which express lacZ widely. Donor-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 α-actinin, and lack of expression of CD45. Donor-derived endothelial cells were identified by expression of lacZ and Flt-1, an endothelial marker shown to be absent on SP cells. Endothelial engraftment was found at a prevalence of around 3.3%, primarily in small vessels adjacent to the infarct. Our results demonstrate the cardiomyogenic potential of hematopoietic stem cells and suggest a therapeutic strategy that eventually could benefit patients with myocardial infarction.