After myocardial injury, cardiomyocyte loss cannot be corrected by using currently available clinical treatments. In recent years, considerable effort has been made to develop cell-based cardiac repair therapies aimed at correcting for this loss. An exciting crop of recent studies reveals that inducing endogenous repair and proliferation of cardiomyocytes may be a viable option for regenerating injured myocardium. Here, we review current heart failure treatments, the state of cardiomyocyte renewal in mammals, and the molecular signals that stimulate cardiomyocyte proliferation. These signals include growth factors, intrinsic signaling pathways, microRNAs, and cell cycle regulators. Animal model cardiac regeneration studies reveal that modulation of exogenous and cell-intrinsic signaling pathways can induce reentry of adult cardiomyocytes into the cell cycle. Using direct myocardial injection, epicardial patch delivery, or systemic administration of growth molecules, these studies show that inducing endogenous cardiomyocytes to self-renew is an exciting and promising therapeutic strategy to treat cardiac injury in humans.
Keywords: adult; heart failure; myocardium; ploidy; regeneration.