Direct Reprogramming as a Novel Approach for Cardiovascular Regeneration

Abstract

Direct cellular reprogramming provides a new strategy for tissue regeneration, especially to the adult heart. However, endogenous cardiomyocytes have limited regenerative capacity. Since our first report of direct cardiac reprogramming from cardiac fibroblasts with three cardiac developmental transcriptional factors (Gata4, Mef2c, and Tbx5), numerous international studies have been reported to reveal the molecular mechanisms of cardiac reprogramming and improve the efficiency of this nascent technology for cardiac regenerative medicine. These advancements include additional transcriptional factors, microRNAs, epigenetic factors, secreted factors, and cellular microenvironment. Cardiac reprogramming of human fibroblasts has also improved. Although direct cardiac reprogramming may resolve the difficulties in applying induced pluripotent stem cells for cardiac regeneration, numerous challenges remain for future clinical application. In this review, we will provide an update on recent advances in research on direct cardiac reprogramming and discuss the perspectives and challenges of this technology in clinical applications.