Regenerative medicine for the heart: Perspectives on stem-cell therapy

Significance: Despite decades of progress in cardiovascular biology and medicine, heart disease remains the leading cause of death, and there is no cure for the failing heart. Since heart failure is mostly caused by loss or dysfunction of cardiomyocytes (CMs), replacing dead or damaged CMs with new CMs might be an ideal way to reverse the disease. However, the adult heart is composed mainly of terminally differentiated CMs that have no significant self-regeneration capacity. Recent Advances: Stem cells have tremendous regenerative potential and, thus, current cardiac regenerative research has focused on developing stem cell sources to repair damaged myocardium. Critical Issues: In this review, we examine the potential sources of cells that could be used for heart therapies, including embryonic stem cells and induced pluripotent stem cells, as well as alternative methods for activating the endogenous regenerative mechanisms of the heart via transdifferentiation and cell reprogramming. We also discuss the current state of knowledge of cell purification, delivery, and retention. Future Directions: Efforts are underway to improve the current stem cell strategies and methodologies, which will accelerate the development of innovative stem-cell therapies for heart regeneration. Antioxid. Redox Signal. 21, 2018-2031.