Oct4-induced oligodendrocyte progenitor cells enhance functional recovery in spinal cord injury model

EMBO J. 2015 Dec 2;34(23):2971-83. doi: 10.15252/embj.201592652. Epub 2015 Oct 23.

Abstract

The generation of patient-specific oligodendrocyte progenitor cells (OPCs) holds great potential as an expandable cell source for cell replacement therapy as well as drug screening in spinal cord injury or demyelinating diseases. Here, we demonstrate that induced OPCs (iOPCs) can be directly derived from adult mouse fibroblasts by Oct4-mediated direct reprogramming, using anchorage-independent growth to ensure high purity. Homogeneous iOPCs exhibit typical small-bipolar morphology, maintain their self-renewal capacity and OPC marker expression for more than 31 passages, share high similarity in the global gene expression profile to wild-type OPCs, and give rise to mature oligodendrocytes and astrocytes in vitro and in vivo. Notably, transplanted iOPCs contribute to functional recovery in a spinal cord injury (SCI) model without tumor formation. This study provides a simple strategy to generate functional self-renewing iOPCs and yields insights for the in-depth study of demyelination and regenerative medicine.

Keywords: Oct4; direct conversion; myelination; oligodendrocyte progenitor cell; self‐renewal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Fibroblasts / cytology
  • Immunohistochemistry
  • Karyotype
  • Male
  • Mice
  • Mice, SCID
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism*
  • Oligodendroglia / physiology*
  • Rats
  • Recovery of Function / physiology
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / therapy*
  • Stem Cell Transplantation
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stem Cells / physiology

Substances

  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse

Associated data

  • GEO/GSE52035