Reprogramming of Skeletal Myoblasts for Induction of Pluripotency for Tumor-Free Cardiomyogenesis in the Infarcted Heart

Rationale: Skeletal myoblasts (SMs) with inherent myogenic properties are better candidates for reprogramming to pluripotency. Objective: To reprogram SMs to pluripotency and show that reprogrammed SMs (SiPS) express embryonic gene and microRNA profiles and that transplantation of predifferentiated cardiac progenitors reduce tumor formation. Methods and Results: The pMXs vector containing mouse cDNAs for Yamanaka's quarter of stemness factors were used for transduction of SMs purified from male Oct4-GFP(+) transgenic mouse. Three weeks later, GFP(+) expressed formation yielded beating cardiomyocyte-like cells, which expressed early and late cardiac-specific markers. SiPS also had an microRNA profile that was altered during their cardiomyogenic differentiation. Noticeable miR-200a-c was observed in SiPS and SiPS-derived cardiomyocytes, respectively. In vivo studies in an experimental model of acute myocardial infarction showed in DMEM without cells (group 1), SMs (group-2), SiPS (group-3), and SiPS-derived group 4 with attenuated infarct size and improved cardiac function without tumorgenesis. Conclusions: Successful reprogramming was achieved in SMs with ES cell-like microRNA profile. Given the tumorgenic nature of SiPS, their predifferentiation into cardiomyocytes would be important for tumor-free cardiogenesis in the heart. (Circ Res. 2011;109:60-70.)