间充质干细胞
医学
骨关节炎
背根神经节
感觉神经元
神经元
感觉系统
运动神经元
伤害感受器
神经科学
病理
解剖
内科学
背
生物
伤害
中枢神经系统
受体
替代医学
精神科
疾病
作者
Minji Ai,William Edward Hotham,Luke A. Pattison,Qingxi Ma,Frances Henson,Ewan St. John Smith
摘要
Objective Mesenchymal stem/stromal cells (MSCs) and MSC‐derived extracellular vesicles (MSC‐EVs) have been reported to alleviate pain in patients with knee osteoarthritis (OA). We undertook this study to determine whether MSCs and/or MSC‐EVs reduce OA pain through influencing sensory neuron excitability in OA joints. Methods We induced knee OA in adult male C57BL/6J mice through destabilization of the medial meniscus (DMM) surgery. Mice were sorted into 4 experimental groups with 9 mice per group as follows: unoperated sham, untreated DMM, DMM plus MSC treatment, and DMM plus MSC‐EV treatment. Treated mice received either MSCs at week 14 postsurgery or MSC‐EVs at weeks 12 and 14 postsurgery. Mouse behavior was evaluated by digging and rotarod tests and the Digital Ventilated Cage system. At week 16, mouse knee joints were harvested for histology, and dorsal root ganglion (DRG) neurons were isolated for electrophysiology. Furthermore, we induced hyperexcitability in DRG neurons in vitro using nerve growth factor (NGF) then treated these neurons with or without MSC‐EVs and evaluated neuron excitability. Results MSC‐ and MSC‐EV–treated DMM‐operated mice did not display pain‐related behavior changes (in locomotion, digging, and sleep) that occurred in untreated DMM‐operated mice. The absence of pain‐related behaviors in MSC‐ and MSC‐EV–treated mice was not the result of reduced joint damage but rather a lack of knee‐innervating sensory neuron hyperexcitability that was observed in untreated DMM‐operated mice. Furthermore, we found that NGF‐induced sensory neuron hyperexcitability is prevented by MSC‐EV treatment ( P < 0.05 versus untreated NGF‐sensitized neurons when comparing action potential threshold). Conclusion MSCs and MSC‐EVs may reduce pain in OA by direct action on peripheral sensory neurons.
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