Chemical-induced cardiac reprogramming in vivo

Loss or dysfunction of cardiomyocytes lead to heart failure which is a leading cause of death worldwide. 1 It is widely known that the hearts of adult mammals have a very limited regeneration capacity. 2 A number of cell transplantation strategies have been proposed to restore cardiac functions, including the transplantation of primary cardiac progenitor cells (CPCs), or pluripotent stem cell-derived CPC-like, or cardiomyocyte-like cells. 2 However, the former approach suffers from the limited availability of cell sources and the latter has yet to overcome the differentiation efficiency, immune compatibility and possible tumorigenesis problems. 3 Functional cardiomyocytes could also be generated by direct reprogramming of non-muscle cells with forced expression of cardiac transcription factors or microRNAs. 4 More interestingly, cardiomyocytes could be induced from non-myocytes in the heart in vivo by local delivery of transcription factors Gata4, Mef2c , and Tbx5 after coronary ligation. 5 However, viral vector-carried transcription factors are still not favorable in therapeutic applications. 6