Gingiva-Derived Mesenchymal Stem Cell-Extracellular Vesicles Activate Schwann Cell Repair Phenotype and Promote Nerve Regeneration

Tissue Eng Part A. 2019 Jun;25(11-12):887-900. doi: 10.1089/ten.TEA.2018.0176. Epub 2018 Dec 28.

Abstract

Peripheral nerve injuries (PNIs) are common and debilitating, usually resulting in considerable long-term disability and remaining an unmet clinical need. Even though the combination of mesenchymal stem cells (MSCs) and the state-of-the-art tissue engineering technologies has shown promising therapeutic potentials for PNI, there is still not a single licensed stem cell-based product for peripheral nerve repair/regeneration. Emerging evidence indicates that MSC-derived extracellular vesicles (EVs) are comparably effective as MSCs in the therapy of a variety of disease models or pathological conditions. This report shows that local delivery of gingiva-derived mesenchymal stem cell (GMSC)-derived EVs could obviously promote axonal regeneration and functional recovery of injured mice sciatic nerves. Importantly, the findings suggest that GMSC-derived EVs promoted the expression of Schwann cell dedifferentiation/repair phenotype-related genes in vitro, particularly c-JUN, a key transcription factor that drives the activation of repair phenotype of Schwann cells during PNI and regeneration.

Keywords: GMSCs; Schwann cell; dedifferentiation; extracellular vesicles; peripheral nerve injury; repair phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Extracellular Vesicles / metabolism
  • Extracellular Vesicles / pathology
  • Extracellular Vesicles / transplantation*
  • Female
  • Gingiva / metabolism*
  • Gingiva / pathology
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Mice
  • Nerve Regeneration*
  • Peripheral Nerve Injuries* / metabolism
  • Peripheral Nerve Injuries* / pathology
  • Peripheral Nerve Injuries* / therapy
  • Rats
  • Rats, Sprague-Dawley
  • Schwann Cells / metabolism*
  • Schwann Cells / pathology
  • Sciatic Nerve* / injuries
  • Sciatic Nerve* / physiology