Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University School of Medicine, Huangshi, 435003, China.
Clinical Medicine Eight-year Program, 02 Class, 17 Grade, Xiangya School of Medicine, Central South University, Changsha, 410013, China.
CNS Neurol Disord Drug Targets. 2024;23(5):656-673. doi: 10.2174/1871527322666230418090857.
Spinal cord injury (SCI) is an intractable and poorly prognostic neurological disease, and current treatments are still unable to cure it completely and avoid sequelae. Extracellular vesicles (EVs), as important carriers of intercellular communication and pharmacological effects, are considered to be the most promising candidates for SCI therapy because of their low toxicity and immunogenicity, their ability to encapsulate endogenous bioactive molecules (e.g., proteins, lipids, and nucleic acids), and their ability to cross the blood-brain/cerebrospinal barriers. However, poor targeting, low retention rate, and limited therapeutic efficacy of natural EVs have bottlenecked EVs-based SCI therapy. A new paradigm for SCI treatment will be provided by engineering modified EVs. Furthermore, our limited understanding of the role of EVs in SCI pathology hinders the rational design of novel EVbased therapeutic approaches. In this study, we review the pathophysiology after SCI, especially the multicellular EVs-mediated crosstalk; briefly describe the shift from cellular to cell-free therapies for SCI treatment; discuss and analyze the issues related to the route and dose of EVs administration; summarize and present the common strategies for EVs drug loading in the treatment of SCI and point out the shortcomings of these drug loading methods; finally, we analyze and highlight the feasibility and advantages of bio-scaffold-encapsulated EVs for SCI treatment, providing scalable insights into cell-free therapy for SCI.
脊髓损伤（SCI）是一种棘手且预后不良的神经疾病，目前的治疗方法仍无法完全治愈该病并避免后遗症。细胞外囊泡（EVs）作为细胞间通讯和药理作用的重要载体，由于其低毒性和免疫原性、封装内源性生物活性分子（如蛋白质、脂质和核酸）的能力以及穿越血脑/脑脊液屏障的能力，被认为是治疗 SCI 最有前途的候选药物。然而，天然 EVs 的靶向性差、保留率低和治疗效果有限，这限制了基于 EVs 的 SCI 治疗。工程化修饰的 EVs 将为 SCI 治疗提供新的范例。此外，我们对 EVs 在 SCI 病理中的作用的认识有限，阻碍了新型 EV 治疗方法的合理设计。在本研究中，我们综述了 SCI 后的病理生理学，特别是多细胞 EVs 介导的串扰；简要描述了从细胞治疗向细胞外无细胞治疗治疗 SCI 的转变；讨论和分析了与 EVs 给药途径和剂量相关的问题；总结和介绍了用于 SCI 治疗的 EVs 药物装载的常见策略，并指出这些药物装载方法的缺点；最后，我们分析并强调了生物支架包封的 EVs 用于 SCI 治疗的可行性和优势，为 SCI 的无细胞治疗提供了可扩展的见解。
