Mending the Heart Through In Situ Cardiac Regeneration

The mammalian heart has limited capacity for repair, and cardiomyocyte loss due to injury results in heart failure and death. Reports have suggested that cardiomyogenesis in the adult mammalian heart is still feasible through the manipulation of existing signaling pathways, which otherwise prevent cardiac regeneration from occurring. This has ignited an intense interest by groups attempting to understand the intrinsic cardiac regenerative capacity with a goal of manipulating it to activate a robust cardiac regeneration response, regain sufficient cardiac functional output, and ultimately improve the patient's life quality. Current strategies described here focus on (1) inducing cardiomyocytes to proliferate generating nascent functional contractile cells; (2) delivering cell progenitors with the capacity to differentiate into cardiomyocytes or vasculature; (3) activating intrinsic populations of cell progenitors or recruiting systemic cells to the myocardium; (4) genetically engineering the induction of regeneration in the existing myocardium; and (5) transdifferentiating cardiac nonmyocytes into cardiomyocytes.