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Curr Mol Med. 2019;19(2):77-90. doi: 10.2174/1566524019666190325113945.

A Revolution in Reprogramming: Small Molecules.

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Shanghai Children's Medical Center, Shanghai Jiaotong University, School of Medicine, Shanghai, China.


Transplantation of reprogrammed cells from accessible sources and in vivo reprogramming are potential therapies for regenerative medicine. During the last decade, genetic approaches, which mostly involved transcription factors and microRNAs, have been shown to affect cell fates. However, their potential carcinogenicity and other unexpected effects limit their translation into clinical applications. Recently, with the power of modern biology-oriented design and synthetic chemistry, as well as high-throughput screening technology, small molecules have been shown to enhance reprogramming efficiency, replace genetic factors, and help elucidate the molecular mechanisms underlying cellular plasticity and degenerative diseases. As a non-viral and non-integrating approach, small molecules not only show revolutionary capacities in generating desired exogenous cell types but also have potential as drugs that can restore tissues through repairing or reprogramming endogenous cells. Here, we focus on the recent progress made to use small molecules in cell reprogramming along with some related mechanisms to elucidate these issues.


Small molecules; chemical compounds; regenerative medicine; reprogramming; stem cells; transdifferentiation.

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