Conversion of Human Fibroblasts into Induced Neural Stem Cells by Small Molecules

Int J Mol Sci. 2022 Feb 3;23(3):1740. doi: 10.3390/ijms23031740.

Abstract

Induced neural stem cells (iNSCs) reprogrammed from somatic cells hold great potentials for drug discovery, disease modelling and the treatment of neurological diseases. Although studies have shown that human somatic cells can be converted into iNSCs by introducing transcription factors, these iNSCs are unlikely to be used for clinical application due to the safety concern of using exogenous genes and viral transduction vectors. Here, we report the successful conversion of human fibroblasts into iNSCs using a cocktail of small molecules. Furthermore, our results demonstrate that these human iNSCs (hiNSCs) have similar gene expression profiles to bona fide NSCs, can proliferate, and are capable of differentiating into glial cells and functional neurons. This study collectively describes a novel approach based on small molecules to produce hiNSCs from human fibroblasts, which may be useful for both research and therapeutic purposes.

Keywords: human fibroblasts; induced neuron stem cells; small molecules.

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Biomarkers / metabolism
  • Cell Differentiation* / drug effects
  • Cell Differentiation* / genetics
  • Cell Line
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Electrophysiological Phenomena
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Mice
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Oligodendroglia / cytology
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism
  • Small Molecule Libraries / pharmacology*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Biomarkers
  • Small Molecule Libraries