Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury

J Neurosci. 2005 May 11;25(19):4694-705. doi: 10.1523/JNEUROSCI.0311-05.2005.

Abstract

Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Bromodeoxyuridine / metabolism
  • Cell Count / methods
  • Cell Differentiation / physiology
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Female
  • Fibroblasts / physiology
  • Glial Fibrillary Acidic Protein / metabolism
  • High Mobility Group Proteins / metabolism
  • Humans
  • Imaging, Three-Dimensional / methods
  • Immunohistochemistry / methods
  • Locomotion / physiology*
  • Myelin Sheath / physiology*
  • Nerve Tissue Proteins / metabolism
  • Oligodendroglia / physiology*
  • Oligodendroglia / transplantation
  • Oligopeptides / metabolism
  • Phosphopyruvate Hydratase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / physiology*
  • SOXE Transcription Factors
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy*
  • Stem Cell Transplantation*
  • Time Factors
  • Transcription Factors / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • High Mobility Group Proteins
  • Nerve Tissue Proteins
  • Olig1 protein, rat
  • Oligopeptides
  • RNAIII inhibiting peptide
  • SOX10 protein, human
  • SOXE Transcription Factors
  • Sox10 protein, rat
  • Transcription Factors
  • Phosphopyruvate Hydratase
  • Bromodeoxyuridine