Evolving approaches to heart regeneration by therapeutic stimulation of resident cardiomyocyte cell cycle

Heart has long been considered a terminally differentiated organ. Recent studies, however, have suggested that there is a modest degree of cardiomyocyte (CM) turnover in adult mammalian heart, albeit not sufficient for replacement of lost CMs following cardiac injuries. Cardiac regeneration studies in various model organisms including zebrafish, newt, and more recently in neonatal mouse, have demonstrated that CM dedifferentiation and concomitant proliferation play important roles in replacement of lost CMs and restoration of cardiac contractility. Further studies with neonatal cardiac regeneration mouse model suggested that major source of new CMs is existing CMs, with the possibility of involvement of cardiac stem cells. Numerous studies have now been conducted on induction of cardiac regeneration and have identified various cardiogenic factors, cardiogenic micro ribonucleic acid and cardiogenic small molecules. This report is a review of studies regarding generation of CM and prospects for application.