Novel Cellular Strategies for Generation of Human Cardiomyocytes in Vitro

The human heart has very limited regenerative capacity, and the low rate of carcinogenesis is not sufficient to compensate for the enormous loss of cells after injury such as myocardial infarction. Despite advances in cardiac treatment, myocardial repair remains severely limited by the lack of an appropriate source of viable cardiomyocytes (CMs) to replace damaged tissue. Human pluripotent stem cells (hPSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can efficiently be differentiated into functional CMs necessary for cell replacement therapy and other potential applications. The number of protocols that derive CMs from hPSCs has increased exponentially over the past decade following observation of the first human beating CMs. A number of highly efficient, chemical based protocols have been developed to generate humanCMs (hCMs) in small-scale and large-scale suspension systems. To reduce the heterogeneity of hPSC-derived CMs, the differentiation protocols were modulated to exclusively generate atrial-, ventricular- and nodal-like CM subtypes. Recently, remarkable advances have been achieved in hCM generation including chemical-based cardiac differentiation, cardiac subtype specification, large-scale suspension culture differentiation, and development of chemically defined culture conditions. All highlight the possibility that hPSC-derived CMs may be very close to implementation in cell-based replacement therapies and other applications. Herein we review recent progress in the in vitro generation of CMs and cardiac subtypes from hPSCs and discuss their potential applications and remaining limitations.

کلیدواژه ها:

Heart Regeneration ، Human Pluripotent Stem Cells ، Direct Reprogramming ، Cell Therapy