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Antinociceptive effect of intrathecal injection of miR-9-5p modified mouse bone marrow mesenchymal stem cells on a mouse model of bone cancer pain

Authors
  • Zhu, Chao1, 2
  • Wang, Kun1
  • Chen, Zhi1
  • Han, Yingchao1
  • Chen, Hao1
  • Li, Quan1
  • Liu, Zude1
  • Qian, Lie1
  • Tang, Jun3
  • Shen, Hongxing1
  • 1 Shanghai Jiao Tong University, Shanghai, 200240, China , Shanghai (China)
  • 2 987 Hospital of PLA, Xi’an, Shaanxi Province, 721000, China , Xi’an (China)
  • 3 Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, Jiangsu, 210002, China , Nanjing (China)
Type
Published Article
Journal
Journal of Neuroinflammation
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Mar 16, 2020
Volume
17
Issue
1
Identifiers
DOI: 10.1186/s12974-020-01765-w
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundA growing body of studies have indicated that bone marrow mesenchymal stem cells (BMSCs) have powerful analgesic effects in animal models of bone cancer pain. Here, we explored the molecular mechanisms underlying how BMSCs alleviate pain sensation in a mouse model of bone cancer pain.MethodsC3H/HeN adult male mice were used to generate a bone cancer pain model. BMSCs were isolated from mouse bone marrow, modified by transfection with microRNA-9-5p (miR-9-5p), and infused into the spinal cord. Spontaneous flinches, paw withdrawal latency, limb-use score, and weight-bearing score were used to assess pain-related behaviors. ELISA, RT-PCR, western blot, and luciferase assay were used to assess gene expressions.ResultsOur results show that miR-9-5p regulated the expression of both repressor element silencing transcription factor (REST) and μ-opioid receptors (MOR) by targeting REST in primary mouse BMSCs. Overexpression of miR-9-5p reversed the activation of inflammatory pathway in TNF-α- and IL-6-treated BMSCs. In addition, miR-9-5p modified BMSCs alleviated cancer pain in the sarcoma-inoculated mouse model. MiR-9-5p modified BMSCs suppressed cytokine expression in the spinal cord of sarcoma-inoculated mice by suppressing REST gene expression.ConclusionsOur results indicate that miR-9-5p modified BMSCs can relieve bone cancer pain via modulating neuroinflammation in the central nervous system, suggesting genetically modified BMSCs could be a promising cell therapy in pain management.

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