Amending the injured heart by in vivo reprogramming

Ischemic heart injury causes death of cardiomyocyte (CM), formation of a fibrotic scar, and often adverse cardiac remodeling, resulting in chronic heart failure. Therapeutic interventions have lowered myocardial damage and improved heart function, but pharmacological treatment of heart failure has only shown limited progress in recent years. Over the past two decades, different approaches have been pursued to regenerate the heart, by transplantation of newly generated CMs derived from pluripotent stem cells, generation of new CMs by reprogramming of cardiac fibroblasts, or by activating proliferation of preexisting CMs. Here, we summarize recent progress in the development of strategies for in situ generation of new CMs, review recent advances in understanding the underlying mechanisms, and discuss the challenges and future directions of the field.