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Intrathecal administration of human bone marrow mesenchymal stem cells genetically modified with human proenkephalin

Yi Sun, Dengwen Zhang1, Haifeng Li1

  • 1Guangdong General Hospital.

Molecular Pain
|March 23, 2017
PubMed
Summary

Genetically engineered mesenchymal stem cells (MSCs) expressing the human proenkephalin (hPPE) gene effectively reduced neuropathic pain in rats. This hPPE-modified MSC therapy shows promise for treating chronic pain conditions.

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Area of Science:

  • Regenerative Medicine
  • Neuroscience
  • Pain Research

Background:

  • Mesenchymal stem cells (MSCs) are explored for neuropathic pain therapy.
  • Enhancing MSC efficacy via gene modification, specifically with the human proenkephalin (hPPE) gene, is investigated.
  • The study focuses on engineered human bone marrow stem cells (hBMSCs) carrying the hPPE gene (hPPE-hBMSCs).

Purpose of the Study:

  • To investigate the antinociceptive effects of hPPE-hBMSCs.
  • To evaluate the efficacy of hPPE-hBMSCs in a rat model of chronic constriction injury (CCI)-induced neuropathic pain.
  • To assess the impact of hPPE gene transfer on MSC bioactivity.

Main Methods:

  • Primary hBMSCs were cultured and modified with the hPPE gene.
  • Intrathecal injection of 6 × 10^6 hPPE-hBMSCs into rats with CCI.
  • Measurement of paw mechanical withdrawal threshold and thermal latency before and after surgery.
  • In vitro and in vivo analysis of hPPE gene transfer effects on MSC bioactivity.

Main Results:

  • Gene transfer did not alter hBMSC surface phenotypes or differentiation.
  • The hPPE-hBMSC group exhibited improved pain thresholds (mechanical and thermal) on the ipsilateral side starting day 9 post-CCI.
  • The analgesic effect was antagonized by naloxone, confirming opioid receptor involvement.
  • Leucine-enkephalin (L-EK) secretion was significantly increased in the hPPE-engineered hBMSC group.

Conclusions:

  • Intrathecal administration of hPPE gene-modified BMSCs effectively alleviates CCI-induced neuropathic pain in rats.
  • This therapeutic approach holds potential for treating human neuropathic pain.
  • hPPE gene modification enhances the analgesic capacity of BMSCs.