Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration

Int J Mol Sci. 2016 Nov 9;17(11):1867. doi: 10.3390/ijms17111867.

Abstract

Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been performed and has shown promising clinical results for treating nerve injuries and donor site morbidity, and insufficient production of the cells have been considered as a major issue. Here, we performed differentiation of tonsil-derived mesenchymal stem cells (T-MSCs) into SC-like cells (T-MSC-SCs), to evaluate T-MSC-SCs as an alternative to SCs. Using SC markers such as CAD19, GFAP, MBP, NGFR, S100B, and KROX20 during quantitative real-time PCR we detected the upregulation of NGFR, S100B, and KROX20 and the downregulation of CAD19 and MBP at the fully differentiated stage. Furthermore, we found myelination of axons when differentiated SCs were cocultured with mouse dorsal root ganglion neurons. The application of T-MSC-SCs to a mouse model of sciatic nerve injury produced marked improvements in gait and promoted regeneration of damaged nerves. Thus, the transplantation of human T-MSCs might be suitable for assisting in peripheral nerve regeneration.

Keywords: Schwann cell; differentiation; peripheral nerve; regeneration; tonsil-derived mesenchymal stem cells.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation
  • Child
  • Coculture Techniques
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Gene Expression
  • Humans
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nerve Regeneration / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Palatine Tonsil / cytology
  • Palatine Tonsil / metabolism
  • Palatine Tonsil / surgery
  • Peripheral Nerve Injuries / metabolism
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / rehabilitation*
  • Peripheral Nerve Injuries / surgery
  • Recovery of Function
  • Schwann Cells / cytology*
  • Schwann Cells / metabolism
  • Schwann Cells / transplantation
  • Sciatic Nerve / injuries*
  • Sciatic Nerve / metabolism
  • Tonsillectomy
  • Transplantation, Heterologous

Substances

  • Biomarkers
  • Nerve Tissue Proteins