Cardiac Myocyte Progenitors from Adult Hearts for Myocardial Regenerative Therapy

Abstract

The heart is a highly vascular organ and prolonged interruption of myocardial blood flow initiates events that culminate in cardiac myocyte death. Proposed experimental reparative strategies include harvesting potent cells followed by direct injection into ischemic myocardium to achieve myogenesis and angiogenesis. Accordingly, we set out to isolate and expand a purified population of adult rat putative cardiomyocyte precursors, and to identify their characteristics in vitro. By using an acute myocardial infarction model and direct cell implantation, we further tested the hypothesis that these cells are an ideal cell source for myocardial regeneration and can enhance cardiac repair after implantation into the ischemic rat heart. We describe here the identification of a subpopulation of primitive cells from rat heart, processing stem cell marker, c-kit and myogenic transcriptional factors, GATA-4 and MEF 2C, and cardiac specific proteins, troponin-I, alpha-sarcomeric actinin and connexin-43. They exhibited a high in vitro proliferative potential. These findings strongly suggest that these cells are putative cardiomyocyte precursors. After transplantation, they were able to be retained and proliferate (13.63 +/- 5.97% after 2 weeks) within the ischemic heart. Progeny of implanted cells migrated along the infarcted scar, reconstituted regenerated cardiomyocytes with incorporation into host myocardium, and inhibited cardiac remodeling with decreased scar formation. Our findings suggest that putative cardiomyocyte precursors isolated from adult heart could potentially be an autologous cell source for myocardial regeneration cell therapy.