中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (9): 2050-2057.doi: 10.4103/1673-5374.335167

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

聚多巴胺修饰甲壳质小间隙神经套管负载外泌体缓慢释放可促进周围神经的再生

  

  • 出版日期:2022-09-15 发布日期:2022-03-08

Sustained release of exosomes loaded into polydopamine-modified chitin conduits promotes peripheral nerve regeneration in rats

Ci Li1, 2, 3, #, Song-Yang Liu1, 2, 3, #, Meng Zhang1, 2, 3, Wei Pi1, 2, 3, Bo Wang4, Qi-Cheng Li1, 2, 3, Chang-Feng Lu1, 2, 3, Pei-Xun Zhang1, 2, 3, *   

  1. 1Department of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, China; 2Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Beijing, China; 3National Center for Trauma Medicine, Beijing, China; 4Department of Orthopedics, Beijing Jishuitan Hospital, Beijing, China
  • Online:2022-09-15 Published:2022-03-08
  • Contact: Pei-Xun Zhang, PhD, zhangpeixun@bjmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 31771322, 31571235; the National Science Foundation of Beijing, No. 7212121; Beijing Science Technology New Star Cross Subject, No. 2018019; Science and Technology Plan Project of Shenzhen, No. JCYJ 20190806162205278; the Key Laboratory of Trauma and Neural Regeneration (Peking University), Ministry of Education; and a grant from National Center for Trauma Medicine, No. BMU2020XY005-01 (all to PXZ).

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摘要：

来源于间充质干细胞的外泌体由于在细胞间通讯和生物调节中的重要作用，因而越来越受到关注。作者在既往研究的神经导管的基础上，设计了一种可负载大量的间充质干细胞源性外泌体的聚多巴胺修饰的甲壳质小间隙神经套管，并可持续而稳定释放它们。体外实验显示，间充质干细胞源性外泌体可增强许旺细胞的增殖和分泌能力，并促进许旺细胞高表达c-Jun、Sox2基因和低表达MBP和Krox20基因，使细胞重新编程到修复状态，同时还能促进背根神经节神经突的生长。而聚多巴胺修饰的甲壳质小间隙神经套管中的聚多巴胺使得间充质干细胞源性外泌体的神经再生作用更加显著。进一步将负载间充质干细胞源性外泌体的聚多巴胺修饰的甲壳质小间隙神经套管桥接大鼠坐骨神经2 mm缺损中，可见导管中外泌体的缓释显著加速了神经愈合，并改善神经功能。由此证实，负载间充质干细胞源性外泌体的聚多巴胺修饰的甲壳质小间隙神经套管可通过稳定和可持续释放外泌体，促进损伤周围神经功能的恢复。

https://orcid.org/0000-0001-7200-2281 (Pei-Xun Zhang) 

关键词: 周围神经损伤, 神经导管, 修复, 聚多巴胺, 间充质干细胞, 外泌体, 持续释放, 许旺细胞, 重编程, 周围神经再生

Abstract: Exosomes derived from mesenchymal stem cells are of therapeutic interest because of their important role in intracellular communication and biological regulation. On the basis of previously studied nerve conduits, we designed a polydopamine-modified chitin conduit loaded with mesenchymal stem cell-derived exosomes that release the exosomes in a sustained and stable manner. In vitro experiments revealed that rat mesenchymal stem cell-derived exosomes enhanced Schwann cell proliferation and secretion of neurotrophic and growth factors, increased the expression of Jun and Sox2 genes, decreased the expression of Mbp and Krox20 genes in Schwann cells, and reprogrammed Schwann cells to a repair phenotype. Furthermore, mesenchymal stem cell-derived exosomes promoted neurite growth of dorsal root ganglia. The polydopamine-modified chitin conduits loaded with mesenchymal stem cell-derived exosomes were used to bridge 2 mm rat sciatic nerve defects. Sustained release of exosomes greatly accelerated nerve healing and improved nerve function. These findings confirm that sustained release of mesenchymal stem cell-derived exosomes loaded into polydopamine-modified chitin conduits promotes the functional recovery of injured peripheral nerves.

Key words: exosome, mesenchymal stem cells, modification strategy, nerve conduits, peripheral nerve injury, peripheral nerve regeneration, polydopamine, reprogramming state, Schwann cells, sustained release