Harnessing cell pluripotency for cardiovascular regenerative medicine

Human pluripotent stem cells (hPSCs), in particular embryonic stem cells and induced pluripotent stem cells, have received enormous attention in cardiovascular regenerative medicine owing to their ability to expand and differentiate into functional cardiomyocytes and other cardiovascular cell types. Despite the potential applications of hPSCs for tissue regeneration in patients suffering from cardiovascular disease, whether hPSC-based therapies can be safe and efficacious remains inconclusive, with strong evidence from clinical trials lacking. Critical factors limiting therapeutic efficacy are the degree of maturity and purity of the hPSC-derived differentiated progeny, and the tumorigenic risk associated with residual undifferentiated cells. In this Review, we discuss recent advances in cardiac-cell differentiation from hPSCs and in the direct reprogramming of non-myocyte cells for cardiovascular regenerative applications. We also discuss approaches for the delivery of cells to diseased tissue, and how such advances are contributing to progress in cardiac tissue engineering for tackling heart disease.