Progress and Challenge of Cardiac Regeneration to Treat Heart Failure

Cardiac muscle has limited proliferative capacity, and regenerative therapies are highly in demand as a new treatment strategy. Pharmacological and non-pharmacological therapies have been developed, but these medical therapies have limited effects to cure patients with severe heart failure. Moreover, heart transplantation is limited due to the low number of donor organs. Thus, heart regeneration holds great potential to offer innovative therapy to treat heart failure patients. Currently, there are several strategies for heart regeneration. Transplantation of somatic stem cells was safe and modestly improved cardiac function after myocardial infarction mainly through paracrine mechanisms. Alternatively, new cardiomyocytes could be generated from induced pluripotent stem cells (iPSCs) to transplant into injured hearts. However, several issues remain to be resolved prior to using iPSC-derived cardiomyocytes, such as a potential risk of tumorigenesis and poor survival of transplanted cells in the injured heart. More recently, direct cardiac reprogramming has emerged as a novel technology to regenerate damaged myocardium by directly converting endogenous cardiac fibroblasts into induced cardiomyocyte-like cells to restore cardiac function. Following our first report of cardiac reprogramming, an improvement in cardiac reprogramming efficiency, in vivo direct cardiac reprogramming, and cardiac reprogramming in human cells were reported by many investigators. While these previous studies have advanced regenerative research, many challenges remain. Here, we review the current status of cardiac regenerative technology, a great hope to treat cardiovascular diseases.