Small-molecule-mediated reprogramming: a silver lining for regenerative medicine

Exp Mol Med. 2020 Feb;52(2):213-226. doi: 10.1038/s12276-020-0383-3. Epub 2020 Feb 20.

Abstract

Techniques for reprogramming somatic cells create new opportunities for drug screening, disease modeling, artificial organ development, and cell therapy. The development of reprogramming techniques has grown exponentially since the discovery of induced pluripotent stem cells (iPSCs) by the transduction of four factors (OCT3/4, SOX2, c-MYC, and KLF4) in mouse embryonic fibroblasts. Initial studies on iPSCs led to direct-conversion techniques using transcription factors expressed mainly in target cells. However, reprogramming transcription factors with a virus risks integrating viral DNA and can be complicated by oncogenes. To address these problems, many researchers are developing reprogramming methods that use clinically applicable small molecules and growth factors. This review summarizes research trends in reprogramming cells using small molecules and growth factors, including their modes of action.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cellular Reprogramming / drug effects*
  • Fibroblasts / drug effects
  • Humans
  • Induced Pluripotent Stem Cells / drug effects
  • Kruppel-Like Factor 4
  • Mice
  • Regenerative Medicine / methods
  • Small Molecule Libraries / pharmacology*
  • Transcription Factors / metabolism

Substances

  • KLF4 protein, human
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Small Molecule Libraries
  • Transcription Factors