Understanding Intracellular Signaling Advances Cardiac Reprogramming Technology Toward Clinical Applications.

Abstract

Akt1/Protein Kinase B Enhances Transcriptional Reprogramming of Fibroblasts to Functional Cardiomyocytes Zhou et al Proc Natl Acad Sci U S A. 2015;112:11864–11869. The direct reprogramming of fibroblasts into functional cardiac myocytes is expected to bring new cell therapies for heart failure. Already, essential transcription factors for the reprogramming have been identified. However, several obstacles must be overcome before this technology benefits patients. In particular, there is a need to improve the efficiency of the reprogramming, especially with regards to acquiring mature cardiomyocytes. A recent article in Proceedings of the National Academy of Sciences suggests that the reprogramming can be enhanced with the addition of a kinase, Akt, to the induction protocol . Many experimental cell therapies for heart failure aim to recover the number of functional cardiomyocytes lost. To achieve this purpose, direct conversion methods using transcription factors are being investigated. The first such method was reported by Weintraub et al, who converted fibroblasts into skeletal muscle cells using a single master transcriptional factor, MyoD.1 Almost 2 decades later, a combination of transcriptional factors was discovered to reprogram somatic cells into pluripotent stem cells in mice and humans.2–4 These discoveries demonstrated the high plasticity of cell fate and suggested that any given …