Direct cardiac reprogramming: basics and future challenges

Heart failure is the leading cause of morbidity and mortality worldwide and is characterized by reduced cardiac function. Currently, cardiac transplantation therapy is applied for end-stage heart failure, but it is limited by the number of available donors.

Following an assessment of available literature, a narrative review was conducted to summarizes the current status and challenges of cardiac reprogramming for clinical application. Scientists have developed different regenerative treatment strategies for curing heart failure, including progenitor cell delivery and pluripotent cell delivery. Recently, a novel strategy has emerged that directly reprograms cardiac fibroblast into a functional cardiomyocyte. In this treatment, transcription factors are first identified to reprogram fibroblast into a cardiomyocyte. After that, microRNA and small molecules show great potential to optimize the reprogramming process. Some challenges regarding cell reprogramming in humans are conversion efficiency, virus utilization, immature and heterogenous induced cardiomyocytes, technical reproducibility issues, and physiological effects of depleted fibroblasts on myocardial tissue.

Several strategies have shown positive results in direct cardiac reprogramming. However, direct cardiac reprogramming still needs improvement if it is used as a mainstay therapy in humans, and challenges need to be overcome before cardiac reprogramming can be considered a viable therapeutic strategy. Further advances in cardiac reprogramming studies are needed in cardiac regenerative therapy.