Adult Neural Progenitor Cells Transplanted into Spinal Cord Injury Differentiate into Oligodendrocytes, Enhance Myelination, and Contribute to Recovery

Stem Cell Reports. 2019 May 14;12(5):950-966. doi: 10.1016/j.stemcr.2019.03.013. Epub 2019 Apr 25.

Abstract

Long-term survival and integration of neural progenitor cells (NPCs) transplanted following spinal cord injury (SCI) have been observed. However, questions concerning the differentiation choice, the mechanism of action, and the contribution of NPCs to functional recovery remains unanswered. Therefore, we investigated the differentiation of NPCs, global transcriptomal changes in transplanted NPCs, the effect of NPCs on neuroinflammation, and the causality between NPC transplantation and functional recovery. We found that NPCs transplanted following SCI differentiate mainly into oligodendrocytes and enhance myelination, upregulate genes related to synaptic signaling and mitochondrial activity, and downregulate genes related to cytokine production and immune system response. NPCs suppress the expression of pro-inflammatory cytokines/chemokines; moreover, NPC ablation confirm that NPCs were responsible for enhanced recovery in hindlimb locomotor function. Understanding the reaction of transplanted NPCs is important for exploiting their full potential. Existence of causality implies that NPCs are useful in the treatment of SCI.

Keywords: global transcriptomal changes; hindlimb locomotor function; myelination; neural progenitor cells; neuroinflammation; oligodendrocyte; regeneration; spinal cord injury; transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Gene Expression Profiling / methods
  • Myelin Sheath / metabolism*
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neurons / metabolism
  • Oligodendroglia / cytology*
  • Oligodendroglia / metabolism
  • Rats, Inbred Lew
  • Rats, Transgenic
  • Recovery of Function / physiology
  • Spinal Cord / cytology
  • Spinal Cord / metabolism
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy*
  • Stem Cell Transplantation / methods*

Substances

  • Cytokines