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

Publication Type:

Journal Article

Source:

Stem cells and development, Volume 22, Issue 13, p.1932-1943 (2013)

Keywords:

2013, Center-Authored Paper, Clinical Research Division, February 2013

Abstract:

Platelet-derived growth factors (PDGFs) and their tyrosine kinase receptors play instrumental roles in embryonic organogenesis and diseases of adult organs. In particular, PDGFRα is expressed by multi-potent cardiovascular progenitors in mouse and human embryonic stem cell systems. Although cardiac PDGFRα expression has been studied in multiple species, little is known about its expression in the human heart. Using immunofluorescence we analyzed PDGFRα 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 PDGFRα. This pattern was consistent for both fetal and adult diseased hearts, although more PDGFRα+ cardiomyocytes were noted in the latter. In vitro differentiation assays were then performed on the PDGFRα+ cell fraction isolated from cardiomyocyte-depleted human fetal hearts. Protocols previously reported to direct differentiation to a cardiomyocyte (5-azacytidine), smooth-muscle (PDGF-BB) or endothelial cell fate (vascular endothelial growth factor [VEGF]) were used. Although no significant cardiomyocyte differentiation was observed, PDGFRα+ cells generated significant numbers of smooth muscle cells (smooth-muscle α-actin+ and smooth-muscle myosin+) and endothelial cells (CD31+). These data suggest that a sub-fraction of the cardiac PDGFRα+ population 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.