The All-Chemical Approach: A Solution for Converting Fibroblasts Into Myocytes.

Abstract

Conversion of Human Fibroblasts Into Functional Cardiomyocytes by Small Molecules Cao et al Science . 2016;352:1216–1220. Converting cardiac fibroblasts to cardiomyocytes has been considered as a regenerative strategy for myocardial infarction and other disorders. Recently, Cao et al1 defined a cocktail of 9 chemical compounds with this capability, increasing the likelihood of clinical success. It has taken a while, but the concept that the terminally differentiated state is immutably stable no longer dominates modern biology. In 1938, Hans Spemann contemplated a fantastical experiment in which transfer of an egg nucleus could redirect a recipient somatic cell to become pluripotent, and Gurdon2 made this a reality in 1958 by converting gut epithelial cells into whole frogs. Inspired by Gurdon et al,2 Takahashi and Yamanaka3 developed the induced pluripotent stem cell (iPSC) technology where 4 transcription factors sufficed in generating PSCs. The last decade has witnessed an explosion in cell fate manipulations. Many somatic cell types were interconverted by the means of transcription factors and epigenetic and cellular pathway modulators. As one of the most difficult cells to regenerate, cardiomyocyte was successfully generated from fibroblasts by introducing cocktails of transcriptions factors.4–7 In a recent article in Science , Cao et al1 reported the successful reprograming of functional cardiomyocytes by small molecules and growth factors. Cao et al1 devised a 3-step protocol. Human foreskin fibroblasts or human …