中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (8): 1841-1846.doi: 10.4103/1673-5374.361533

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

运动锻炼结合脂肪干细胞减轻脊髓损伤后神经病理性疼痛

  

  • 出版日期:2023-08-15 发布日期:2023-02-24
  • 基金资助:
    国家自然科学基金(81971151, 82201360,  82202739);国家自然科学青年基金(82102583);广东省自然科学基金(2020A1515010306);广州市科技计划项目(202102020040);博士后国际引进项目 (YJ20210208);第71批博士后面上项目(2022M713592);广东省区域联合基金(2021A1515110188)支持

Exercise combined with administration of adipose-derived stem cells ameliorates neuropathic pain after spinal cord injury

Xing Cheng1, #, Gu-Ping Mao2, #, Wen-Jie Hu3, #, Zheng-Ran Yu1, 4, #, Yi-Yang Xu2, Wei Chen5, Xiang Li1,  Xiao-Lin Zeng1, Wen-Wu Zhang1, Jie-Wen Chen1, Yong Wan1, *, Le Wang1, *   

  1. 1Department of Spine Surgery, Orthopedic Research Institute, The First Affiliated Hospital of Sun Yat-sen University; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Guangzhou, Guandong Province, China; 2Department of Joint Surgery and Sport Medicine, Orthopedic Research Institute, The First Affiliated Hospital of Sun Yat-sen University; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Guangzhou, Guandong Province, China; 3Department of Rehabilitation Medicine, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guandong Province, China; 4Department of Spine Surgery, Orthopedics Center of Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guandong Province, China; 5State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guandong Province, China
  • Online:2023-08-15 Published:2023-02-24
  • Contact: Yong Wan, PhD, wanyong@mail.sysu.edu.cn; Le Wang, PhD, wangle3@mail.sysu.edu.cn.
  • Supported by:
    This study was supported in part by the National Natural Science Foundation of China, Nos. 81971151 (to YW), 82201360 (to XC), 82102583 (to LW), and 82202739 (to GPM); China Postdoctoral Science Foundation, Nos. YJ20210208 and 2022M713592; Guangdong Basic and Applied Basic Research Foundation, China, No. 2021A1515110188 (to XC); the Natural Science Foundation of Guangdong Province, China, No. 2020A1515010306 (to LW); the Science and Technology Program of Guangzhou, China, No. 202102020040 (to LW).

摘要:

实验研究表明,运动锻炼和人类脂肪干细胞在脊髓损伤中发挥积极作用;然而,脂肪干细胞和/或运动是否对脊髓损伤后的神经性疼痛有积极作用仍不清楚。因此,实验建立了一个胸11(T11)脊髓挫伤小鼠模型。脊髓损伤后立即将近1×105个细胞移植到T11脊髓病变部位。受伤后7到28天进行运动锻炼,与单一运动锻炼或脂肪干细胞治疗相比,运动锻炼结合脂肪干细胞治疗可明显缓解脊髓损伤后神经病理性疼痛,有效改善脊髓损伤后的运动功能恢复。另外,运动锻炼结合脂肪干细胞可显著降低小鼠脊髓损伤平面以下的腰髓背角小胶质细胞标志物离子化钙结合接头分子1和星型胶质细胞标志物胶质纤维酸性蛋白的表达。这一发现为临床上脊髓损伤后的疼痛管理及康复治疗提供了新的治疗思路。

https://orcid.org/0000-0001-9633-7326 (Le Wang); https://orcid.org/0000-0002-1008-8072 (Yong Wan)

Abstract: Experimental studies have shown that exercise and human adipose-derived stem cells (ADSCs) play positive roles in spinal cord injury (SCI). However, whether ADSCs and/or exercise have a positive effect on SCI-induced neuropathic pain is still unclear. Thus, there is a need to explore the effects of exercise combined with administration of ADSCs on neuropathic pain after SCI. In this study, a thoracic 11 (T11) SCI contusion model was established in adult C57BL/6 mice. Exercise was initiated from 7 days post-injury and continued to 28 days post-injury, and approximately 1 × 105 ADSCs were transplanted into the T11 spinal cord lesion site immediately after SCI. Motor function and neuropathic pain-related behaviors were assessed weekly using the Basso Mouse Scale, von Frey filament test, Hargreaves method, and cold plate test. Histological studies (Eriochrome cyanine staining and immunohistochemistry) were performed at the end of the experiment (28 days post-injury). Exercise combined with administration of ADSCs partially improved early motor function (7, 14, and 21 days post-injury), mechanical allodynia, mechanical hypoalgesia, thermal hyperalgesia, and thermal hypoalgesia. Administration of ADSCs reduced white and gray matter loss at the lesion site. In addition, fewer microglia and astrocytes (as identified by expression of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein, respectively) were present in the lumbar dorsal horn in the SCI + ADSCs and SCI + exercise + ADSCs groups compared with the sham group. Our findings suggest that exercise combined with administration of ADSCs is beneficial for the early recovery of motor function and could partially ameliorate SCI-induced neuropathic pain. 

Key words: adipose-derived stem cells, allodynia, exercise, glial fibrillary acidic protein, hyperalgesia, hypoalgesia, ionized calcium-binding adapter molecule 1, motor function, spinal cord injury