Human pluripotent stem cell-derived cardiovascular progenitors for heart regeneration

During normal development, cardiac progenitor cells (CPCs) in the pharyngeal mesoderm migrate and contribute to formation of the heart tube. Characterization of the signals that maintain, expand and regulate migration and differentiation of CPCs is essential for understanding the etiology of congenital heart diseases and the potential to differentiate pluripotent stem cells (PSCs) into CPCs for cardiac repair. Although the intricate mechanisms of cardiogenesis are being gradually unraveled, recent clinical and preclinical research studies underscore that full restoration of myocardial structure and function following pathological injuries or aging remains a daunting challenge. Here, we discuss the innate capacity for cardiac regeneration in zebrafish, the types of progenitors driving development in the mammalian heart and how to empower CPCs or myocytes derived from human PSCs to survive, engraft and improve function in the hostile microenvironment of the post-ischemic heart.