Progenitor Cells Identified by PDGFR-Alpha Expression in the Developing and Diseased Human Heart

Platelet-derived growth factors (PDGFs) and their tyrosine kinase receptors play instrumental roles in embryonic organogenesis and diseases of adult organs. In particular, platelet-derived growth factor receptor-alpha (PDGFR alpha) is expressed by multipotent cardiovascular progenitors in mouse and human embryonic stem cell systems. Although cardiac PDGFR alpha expression has been studied in multiple species, little is known about its expression in the human heart. Using immunofluorescence, we analyzed PDGFR alpha expression in both human fetal and diseased adult hearts, finding strong expression in the interstitial cells of the epicardium, myocardium, and endocardium, as well as the coronary smooth muscle. Only rare endothelial cells and cardiomyocytes expressed PDGFR alpha. This pattern was consistent for both the fetal and adult diseased hearts, although more PDGFRa alpha+ cardiomyocytes were noted in the latter. In vitro differentiation assays were then performed on the PDGFR alpha+ cell fraction isolated from the cardiomyocyte-depleted human fetal hearts. Protocols previously reported to direct differentiation to a cardiomyocyte (5-azacytidine), smooth muscle (PDGF-BB), or endothelial cell fates (vascular endothelial growth factor [VEGF]) were used. Although no significant cardiomyocyte differentiation was observed, PDGFR alpha+ cells generated significant numbers of smooth muscle cells (smooth muscle-alpha-actin+ and smooth muscle myosin +) and endothelial cells (CD31 +). These data suggest that a subfraction of the cardiac PDGFR alpha+ populations are progenitors contributing predominantly to the vascular and mesenchymal compartments of the human heart. It may be possible to control the fate of these progenitors to promote vascularization or limit fibrosis in the injured heart.