Cardiomyocyte generation using stem cells and directly reprogrammed cells.

Cardiomyocytes are terminally differentiated cells with limited regenerative capacity in the adult heart, making cell replacement therapy an attractive option to repair injured hearts. Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are pluripotent and capable of infinite expansion in vitro, implicating them as ideal cell types for cell replacement therapy. During the past several years, significant advances in iPS cell generation technology, cardiac differentiation, and cell purification protocols were achieved for the development of stem cell-based heart therapies. The discovery of iPS cells has also sparked the novel idea of direct conversion of mature cell types into another cell type without passing through a pluripotent stem cell state. Functional cardiomyocytes could therefore be directly reprogrammed from differentiated somatic cells by transduction of the three cardiac transcription factors, Gata4, Mef2c, and Tbx5. Herein, we review the recent research achievements and discuss future challenges in stem cell-based cardiac generation and direct cardiac reprogramming technology for heart regeneration.