Direct cardiac reprogramming: from developmental biology to cardiac regeneration

Heart disease affects millions worldwide and is a progressive condition involving loss of cardiomyocytes. The human heart has limited endogenous regenerative capacity and is thus an important target for novel regenerative medicine approaches. Although cell-based regenerative therapies hold promise, cellular reprogramming of endogenous cardiac fibroblasts, which represent more than half of the cells in the mammalian heart, may be an attractive alternative strategy for regenerating cardiac muscle. Recent advances leveraging years of developmental biology point to the feasibility of generating de novo cardiomyocyte-like cells from terminally differentiated nonmyocytes in the heart in situ after ischemic damage. Here, we review the progress in cardiac reprogramming methods and consider the opportunities and challenges that lie ahead in refining this technology for regenerative medicine.