Human Mesenchymal Stem Cells Protect Dorsal Root Ganglia from the Neurotoxic Effect of Cisplatin

Anticancer Res. 2015 Oct;35(10):5383-9.

Abstract

Background/aim: Peripheral neurotoxicity is a dose-limiting factor of many chemotherapeutic agents, including cisplatin. Mesenchymal stem cells are promising for the treatment of several neurological disorders, and our aim was to verify the neuroprotective potential of human mesenchymal stem cells (hMSCs) on dorsal root ganglia (DRG) exposed to cisplatin.

Materials and methods: DRG were exposed to different cisplatin concentrations and then co-cultured with hMSCs or with hMSC-conditioned medium.

Results: hMSCs showed a neuroprotective effect on cisplatin-induced death of DRG, mediated by direct contact. Moreover, DRG exhibited an MSC-dependent promotion of neurite outgrowth, in particular at early time points. For this effect, the expression of Neurite Outgrowth Inhibitor (NOGO) and Myelin Associated Glycoprotein (MAG) by hMSCs was pivotal.

Conclusion: hMSCs are a promising tool for reducing the neurotoxic effect of cisplatin.

Keywords: DRG; MAG; MSC; NOGO; cisplatin; neurite elongation; peripheral neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cisplatin / toxicity*
  • Culture Media, Conditioned / pharmacology*
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / physiology*
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / physiology*
  • Myelin Proteins / metabolism
  • Myelin-Associated Glycoprotein / metabolism
  • Neurites / metabolism
  • Nogo Proteins
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Culture Media, Conditioned
  • MAG protein, human
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Nogo Proteins
  • RTN4 protein, human
  • Rtn4 protein, rat
  • Cisplatin