Skin Fibroblast and CPC Primary Cultures Were Established From the Same Human Donors
Somatic cells were reprogrammed into induced pluripotent stem cells (iPSCs) by overexpression of the pluripotency transcription factors Oct4, Sox2, Klf4, and c-Myc. Established iPSCs derived from fibroblasts (Fib-iPSC) and cardiac progenitor cells (CPC-iPSC) were differentiated into cardiomyocytes. Differentiation efficiency was found to be higher in cardiomyocytes derived from CPC-iPSC (CPC-iPSC-CM) compared with Fib-iPSC (Fib-iPSC-CM). In vitro experiments demonstrated that CPC-iPSCs express higher levels of cardiac transcription factors during cardiac differentiation compared with Fib-iPSCs. Epigenetic assessment showed higher methylation in the promoter region of the cardiac transcription factor NKX2-5 in Fib-iPSC-CMs compared with CPC-iPSC-CMs. However, no significant differences in their morphological and electrophysiological properties were observed. In vivo studies using mouse models of myocardial infarction showed comparable therapeutic effects between CPC-iPSC-CM and Fib-iPSC-CM. In summary, whereas epigenetic memory improves cardiac differentiation efficiency in vitro, the in vivo functional recovery following cell transplantation is equivalent.