Reprogramming of Non-myocytes into Cardiomyocyte-like Cells: Challenges and Opportunities

The high global incidence of heart disease drives the need for methods of mending damaged hearts. Direct reprogramming of cardiac fibroblasts into cardiomyocyte-like cells (called iCMs) has been successful in the creation of new muscle cells, in the repair of hearts post-myocardial injury, and therefore has great promise for the clinic. The purpose of this paper is to review and highlight the approaches for and underlying molecular mechanisms of direct cardiac reprogramming.

Single-cell genomics and mechanistic studies have elucidated the stepwise transition of fibroblasts to iCMs as well as the molecular roadblocks that hinder reprogramming. Cardiac fibroblasts are able to be directly reprogrammed, in vitro and in vivo, into induced cardiomyocyte-like cells by the ectopic expression of a combination of transcription factors, microRNAs or small molecules. Recent works have illustrated methods that improve the efficiency of iCM generation and delivery of reprogramming cocktails as well as have revealed the molecular networks governing the reprogramming process. Current studies have also begun to identify and address the additional hurdles in human iCM reprogramming.