Human embryonic stem cell-derived cardiovascular progenitor cells stimulate cardiomyocyte cell cycle activity via activating the PI3K/Akt pathway.

Promoting endogenous cardiomyocyte proliferation is crucial for repairing infarcted hearts. Implantation of human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) promotes healing of infarcted hearts. However, little is known regarding their impact on host cardiomyocyte proliferation. Here, we revealed that hCVPC implantation into mouse infarcted hearts induced dedifferentiation and cell cycle re-entry of host cardiomyocytes, which was further confirmed in vitro by hCVPC-conditioned medium. Mechanistically, the PI3K/Akt signaling pathway mediated hCVPC-induced cardiomyocyte cell cycle re-entry. The findings reveal the novel function of hCVPCs in triggering cardiomyocyte dedifferentiation and cell cycle activation and highlight a strategy utilizing cells at early developmental stages to rejuvenate adult cardiomyocytes.