Schwann Cell Precursors from Human Pluripotent Stem Cells as a Potential Therapeutic Target for Myelin Repair

Stem Cell Reports. 2017 Jun 6;8(6):1714-1726. doi: 10.1016/j.stemcr.2017.04.011. Epub 2017 May 11.

Abstract

Schwann cells play a crucial role in successful nerve repair and regeneration by supporting both axonal growth and myelination. However, the sources of human Schwann cells are limited both for studies of Schwann cell development and biology and for the development of treatments for Schwann cell-associated diseases. Here, we provide a rapid and scalable method to produce self-renewing Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs), using combined sequential treatment with inhibitors of the TGF-β and GSK-3 signaling pathways, and with neuregulin-1 for 18 days under chemically defined conditions. Within 1 week, hPSC-derived SCPs could be differentiated into immature Schwann cells that were functionally confirmed by their secretion of neurotrophic factors and their myelination capacity in vitro and in vivo. We propose that hPSC-derived SCPs are a promising, unlimited source of functional Schwann cells for treating demyelination disorders and injuries to the peripheral nervous system.

Keywords: Schwann cell; Schwann cell precursor; axon regeneration; hPSCs; myelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axons / physiology
  • Cell Differentiation / drug effects
  • Cell Self Renewal
  • Cells, Cultured
  • Cellular Reprogramming
  • Demyelinating Diseases / therapy*
  • GAP-43 Protein / metabolism
  • Humans
  • Neuregulin-1 / pharmacology
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism*
  • Receptor, Nerve Growth Factor / metabolism
  • Regeneration
  • Schwann Cells / cytology
  • Schwann Cells / metabolism
  • Schwann Cells / transplantation*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • GAP-43 Protein
  • Neuregulin-1
  • Receptor, Nerve Growth Factor
  • Transcription Factors