Engineered exosome-based treatment for peripheral nerve regeneration: a narrative review of clinical prospectsYao, Xiaomin1; Zhou, Yuxiang1; Liu, Yingyu2; Jie, Jing3,*; Wan, Xue4,*; Yang, Pengxiang1,* 1Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu Province, China 2Department of Clinical Laboratory, Nantong Health College of Jiangsu Province, Nantong, Jiangsu Province, China 3Department of Clinical Laboratory, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China 4Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA *Correspondence to: Jing Jie, PhD, jiejing1103@126.com; Xue Wan, PhD, wan.xue@mayo.edu; Pengxiang Yang, PhD, E-mail: yangpengxiang@ntu.edu.cn or yangpengxiang@163.com. Funding:This work was supported by the National Natural Science Foundation of China, Nos. 32271389 and 31900987 (both to PY), and Jiangsu Natural Science Foundation, No. BK20230608 (to JJ). This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License (http://creativecommons.org/licenses/by-nc-sa/4.0/), which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. Advanced Technology in Neuroscience 2(3):p 135-143, September 2025. | DOI: 10.4103/ATN.ATN-D-25-00009 With their unique therapeutic properties and amenability to engineering modifications, exosomes are considered a promising tool for treating peripheral nerve injuries. Through genetic engineering or physicochemical modifications, the targeting ability and functionality of exosomes can be further enhanced, enabling efficient delivery of therapeutic molecules and significantly boosting their therapeutic potential. This review aims to explore exosome-based therapies in peripheral nerve repair and their mechanisms and summarizes recent advances in the roles of exosomes in neuroprotection, axonal regeneration, vascular regeneration, and inflammatory modulation. Exosomes act as natural messengers between cells, carrying genetic materials, cytokines, and growth factors that can modulate the local microenvironment and foster peripheral nerve regeneration. Studies have shown that exosomes derived from Schwann cells, macrophages, neurons, and mesenchymal stem cells can all promote axonal regeneration and modulate inflammatory responses through various mechanisms. Compared with cell therapy, exosome therapy offers greater stability and safety, with the ability to traverse biological barriers, presenting new possibilities for regenerative medicine and precision therapy. However, challenges such as the heterogeneity and complexity of exosomes, uncertainty of in vivo distribution and metabolic pathways, and the limitations of targeting remain to be addressed. Future research will focus on the engineering modifications of exosomes to enhance their therapeutic efficiency and targeting precision. 中文摘要 外泌体具有独特的治疗特性,并可进行工程化修饰,因此被认为是治疗周围神经损伤的一种前景广阔的工具。通过基因工程或理化修饰,外泌体的靶向能力和功能可得到进一步增强,从而实现治疗分子的高效递送并显著提高其治疗潜力。文章的目的在于探讨基于外泌体的疗法在周围神经修复中的应用及其作用机制。文章详细阐述了外泌体在神经保护、轴突再生、血管生成和炎症调节等方面的作用。外泌体作为细胞间的天然信使,携带遗传物质、细胞因子和生长因子,能够调节局部微环境,促进周围神经再生。研究表明,来源于施万细胞、巨噬细胞、神经元和间充质干细胞的外泌体均能促进轴突再生,并通过多种机制调节炎症反应。外泌体疗法相较于细胞疗法具有更高的稳定性和安全性,能够跨越生物屏障,为再生医学和精准治疗提供新的可能性。然而,外泌体的异质性和复杂性、体内分布和代谢途径的不明确性以及靶向性的限制等问题仍需解决。未来的研究将重点关注外泌体的工程化改造,以提高其治疗效率和靶向性。 |