中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (11): 3151-3171.doi: 10.4103/NRR.NRR-D-24-00235

• 综述:周围神经损伤修复保护与再生 • 上一篇    下一篇

治疗周围神经损伤的间充质干细胞及外泌体疗法: "现状 "与 "未来之路"

  

  • 出版日期:2025-11-15 发布日期:2025-02-22

Advances in therapies using mesenchymal stem cells and their exosomes for treatment of peripheral nerve injury: state of the art and future perspectives

Fatima Aldali1, #, Chunchu Deng1, #, Mingbo Nie2 , Hong Chen1, *   

  1. 1 Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China;  2 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
  • Online:2025-11-15 Published:2025-02-22
  • Contact: Hong Chen, MD, chenhong1129@hust.edu.cn.
  • Supported by:
    This work was supported by the Key Research and Development Project of Hubei Province of China, 2022BCA028 (to HC).

摘要:

周围神经损伤是指影响大脑和脊髓以外神经的损伤或创伤,导致运动或感觉障碍。尽管目前已能有效地连接断裂的周围神经并提供各种疗法,但感觉或运动功能的恢复仍然有限,对完全神经损伤修复的有效疗法仍然难以实现。间充质干细胞及其外泌体的疗法是一新兴领域,有望增强神经再生和功能。作为对环境具有反应的活细胞,间充质干细胞分泌各种因子和外泌体,即包含蛋白质、微小RNA和来自母体间充质干细胞的mRNA等生物活性分子的纳米级细胞外囊泡。外泌体在细胞间通讯和神经组织功能中发挥着关键作用,比如,促进轴突重新生长、激活许旺细胞、促进血管再生和调节炎症等;且相较于间充质干细胞,外泌体具有更高的稳定性、低免疫原性、靶向递送、高修复能力、低成瘤形成风险和可穿过血脑屏障等优势。间充质干细胞及其来源的外泌体疗法仍处于探索阶段,目前存在的问题有标准化细胞外囊泡收集技术、外泌体的异质性、临床使用的细胞外囊泡生产规模、表征和质量控制、储存和稳定性、生物分布和靶向性、免疫原性和安全性、监管框架、设计良好的临床试验以及成本效益等。文章首先总结了间充质干细胞及其来源的外泌体在周围神经损伤中的研究进展,探讨其潜在机制。然后,概述了间充质干细胞和外泌体的临床试验现状,并对利用间充质干细胞和外泌体的疗法进行比较分析。最后,讨论了间充质干细胞来源外泌体使用的当前限制和挑战,提供潜在的解决方案并指导未来的方向。全面地总结最新的临床前实验和临床试验对于全面理解外泌体相关治疗策略和促进临床转化至关重要。

https://orcid.org/0000-0002-8848-282X (Hong Chen)

Abstract: “Peripheral nerve injury” refers to damage or trauma affecting nerves outside the brain and spinal cord. Peripheral nerve injury results in movements or sensation impairments, and represents a serious public health problem. Although severed peripheral nerves have been effectively joined and various therapies have been offered, recovery of sensory or motor functions remains limited, and efficacious therapies for complete repair of a nerve injury remain elusive. The emerging field of mesenchymal stem cells and their exosome-based therapies hold promise for enhancing nerve regeneration and function. Mesenchymal stem cells, as large living cells responsive to the environment, secrete various factors and exosomes. The latter are nano-sized extracellular vesicles containing bioactive molecules such as proteins, microRNA, and messenger RNA derived from parent mesenchymal stem cells. Exosomes have pivotal roles in cell-to-cell communication and nervous tissue function, offering solutions to changes associated with cell-based therapies. Despite ongoing investigations, mesenchymal stem cells and mesenchymal stem cell– derived exosome-based therapies are in the exploratory stage. A comprehensive review of the latest preclinical experiments and clinical trials is essential for deep understanding of therapeutic strategies and for facilitating clinical translation. This review initially explores current investigations of mesenchymal stem cells and mesenchymal stem cell–derived exosomes in peripheral nerve injury, exploring the underlying mechanisms. Subsequently, it provides an overview of the current status of mesenchymal stem cell and exosomebased therapies in clinical trials, followed by a comparative analysis of therapies utilizing mesenchymal stem cells and exosomes. Finally, the review addresses the limitations and challenges associated with use of mesenchymal stem cell–derived exosomes, offering potential solutions and guiding future directions.

Key words: clinical trials, exosome, extracellular vesicles, mesenchymal stem cells, nerve regeneration, peripheral nerve injury, pre-clinical experiments