Regenerative potential of mouse embryonic stem cell-derived PDGFRα+ cardiac lineage committed cells in infarcted myocardium

BACKGROUND Pluripotent stem cell-derived cardiomyocytes (CMs) have become one of the most attractive cellular resources for cell-based therapy to rescue damaged cardiac tissue. AIM We investigated the regenerative potential of mouse embryonic stem cell (ESC)-derived platelet-derived growth factor receptor-alpha (DGFR alpha)(+) cardiac lineage-committed cells (CLCs), which have a proliferative capacity but are in a morphologically and functionally immature state compared with differentiated CMs. METHODS We induced mouse ESCs into PDGFR alpha(+) CLCs and alpha MHC+ CMs using a combination of the small molecule cyclosporin A, the rho-associated coiled-coil kinase inhibitor Y27632, the antioxidant Trolox, and the ALK5 inhibitor EW7197. We implanted PDGFR alpha(+) CLCs and differentiated alpha MHC+ CMs into a myocardial infarction (MI) murine model and performed functional analysis using transthoracic echocardiography (TTE) and histologic analysis. RESULTS Compared with the untreated MI hearts, the anterior and septal regional wall motion and systolic functional parameters were notably and similarly improved in the MI hearts implanted with PDGFR alpha(+) CLCs and alpha MHC+ CMs based on TTE. In histologic analysis, the untreated MI hearts contained a thinner ventricular wall than did the controls, while the ventricular walls of MI hearts implanted with PDGFR alpha(+) CLCs and alpha MHC+ CMs were similarly thicker compared with that of the untreated MI hearts. Furthermore, implanted PDGFR alpha(+) CLCs aligned and integrated with host CMs and were mostly differentiated into alpha-actinin(+) CMs, and they did not convert into CD31(+) endothelial cells or alpha SMA(+) mural cells. CONCLUSION PDGFR alpha(+) CLCs from mouse ESCs exhibiting proliferative capacity showed a regenerative effect in infarcted myocardium. Therefore, mouse ESC-derived PDGFR alpha(+) CLCs may represent a potential cellular resource for cardiac regeneration.