Loss of terminally differentiated cardiomyocytes due to heart disease is irreversible and current therapeutic regimes are limited. Cell therapy using stem cell-derived cardiomyocytes is an attractive option to repair injured hearts. The discovery of direct reprogramming of fibroblasts into induced pluripotent stem cells (iPSCs) and successful differentiation of iPSCs into cardiomyocytes provided a revolutionary paradigm in heart regenerative research. During the past decades, significant advances in stem cell culture, differentiation and purification protocols, as well as in cell transplantation methodologies, have been achieved. On the other hand, recent studies demonstrated that a somatic cell could be converted into an alternative differentiated cell type without first becoming a stem cell by overexpression of lineage-specific factors. We found that functional cardiomyocytes can be directly induced from fibroblasts by a combination of three cardiac transcription factors, Gata4, Mef2c and Tbx5, in vitro and in vivo. I will review the perspectives of heart regeneration using reprogramming technology.

(Communicated by Hiroo IMURA, M.J.A.)