Intrathecal Injection of Human Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorates Neuropathic Pain in Rats

Neurochem Res. 2016 Dec;41(12):3250-3260. doi: 10.1007/s11064-016-2051-5. Epub 2016 Sep 21.

Abstract

Neuropathic pain (NP) is a clinically incurable disease with miscellaneous causes, complicated mechanisms and available therapies show poor curative effect. Some recent studies have indicated that neuroinflammation plays a vital role in the occurrence and promotion of NP and anti-inflammatory therapy has the potential to relieve the pain. During the past decades, mesenchymal stem cells (MSCs) with properties of multipotentiality, low immunogenicity and anti-inflammatory activity have showed excellent therapeutic effects in cell therapy from animal models to clinical application, thus aroused great attention. However there are no reports about the effect of intrathecal human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on NP which is induced by peripheral nerve injury. Therefore, in this study, intrathecally transplanted HUC-MSCs were utilized to examine the effect on neuropathic pain induced by a rat model with spinal nerve ligation (SNL), so as to explore the possible mechanism of those effects. As shown in the results, the HUC-MSCs transplantation obviously ameliorated SNL-induced mechanical allodynia and thermal hyperalgesia, which was related to the inhibiting process of neuroinflammation, including the suppression of activated astrocytes and microglia, as well as the significant reduction of pro-inflammatory cytokines Interleukin-1β (IL-1β) and Interleukin -17A (IL-17A) and the up-regulation of anti-inflammatory cytokine Interleukin -10 (IL-10). Therefore, through the effect on glial cells, pro-inflammatory and anti-inflammatory cytokine, the targeting intrathecal HUC-MSCs may offer a novel treatment strategy for NP.

Keywords: Astrocyte; Mesenchymal stem cells; Microglia; Neuropathic pain; Spinal nerve ligation.

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Humans
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology
  • Hyperalgesia / therapy
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / therapy
  • Interleukin-10 / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-1beta / metabolism
  • Ligation
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Microglia / metabolism
  • Neuralgia / etiology
  • Neuralgia / physiopathology
  • Neuralgia / therapy*
  • Rats, Sprague-Dawley
  • Spinal Nerves / injuries
  • Umbilical Cord / cytology*

Substances

  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-10