Cardiomyocyte Proliferation for Therapeutic Regeneration

Purpose of review: Current pharmacologic treatments for cardiovascular disease do not correct the underlying cellular defect, the loss of cardiomyocytes. With recent advancements in cardiac regenerative approaches, the induction of endogenous mature cardiomyocyte proliferation has emerged as a new possibility. Here, we review progress made toward the regeneration of cardiac tissue in the mammalian heart through the stimulation of mature cardiomyocyte renewal.

Recent findings: The targeting of several developmental and signaling pathways has been shown to stimulate cell cycle re-entry in mature cardiomyocytes. In animal models of cardiac regeneration, various strategies have been used to target these pathways to stimulate cardiomyocyte renewal and have relied on the delivery of signaling factors via systemic delivery, epicardial patches, or direct intramyocardial injection. Gene therapy techniques involving the viral delivery of transgenes by using adenoviral or adeno-associated viral vectors have been used to successfully target cardiac gene expression. The delivery of nucleic acids in the form of anti-microRNAs and microRNA mimetics has also been shown to be effective in stimulating cardiomyocyte renewal. As the field of cardiac regeneration continues to progress, an important ongoing challenge in developing clinically translatable therapies is limiting the stimulation of growth pathways in non-cardiomyocytes.