外泌体在脊髓损伤中的应用进展  

Research progress of exosomes associated with spinal cord injury

作　　者：潘禹熹 万俊明 Pan Yuxi;Wan Junming(Sun Yat-sen University School of Medicine,Shenzhen 518000,China;Department of Orthopaedic Surgery,Seventh Affiliated Hospital of Sun Yat-senUniversity,Shenzhen518000,China)

机构地区：[1]中山大学医学院,深圳518000 [2]中山大学附属第七医院骨科,深圳1518000

出　　处：《中华骨科杂志》2024年第21期1432-1440,共9页Chinese Journal of Orthopaedics

基　　金：浙江省自然科学基金联合基金项目(LBY21H170001);深圳市科技创新委员会基础研究面上项目(JCYJ20210324122807021);广西骨关节退行性病变基础与转化研究重点实验室开放课题(21-220-06)。

摘　　要：脊髓损伤(spinal cord injury, SCI)可导致严重的感觉与运动功能障碍, 其病理特征为轴索的直接断裂、神经细胞的坏死和凋亡等细胞损伤。目前临床治疗方法较有限。传统的干预措施, 例如药物治疗和细胞治疗, 疗效有限, 预后较差。近年来, 外泌体因其独特的磷脂特性及能够包裹核酸与蛋白质等内含物而成为脊髓损伤修复的新手段。多种细胞可在内体分选复合物蛋白、大鼠肉瘤相关蛋白及脂质等细胞内囊泡运输相关分子的辅助下产生外泌体。这些因继承各自细胞来源的分子组成而具有结构和功能上多样性的外泌体可靶向递送至不同的受体细胞, 在抑制胶质瘢痕形成、减少炎症和促进神经再生修复等方面发挥关键作用。通过明确间充质干细胞、神经干细胞、Schwann细胞等来源外泌体对脊髓损伤修复的作用靶点, 可根据患者损伤类型的特定细胞和分子背景进行个体化治疗, 从而优化治疗的有效性与安全性。但外泌体的临床应用尚存在诸如循环清除较快, 难以长期维持损伤部位的治疗浓度, 缺乏兼顾分离效率与特异性的分离纯化手段, 难以满足临床需求等限制。在国际细胞外囊泡学会总结的分离提纯手段的基础上, 学者们目前常用的解决方案包括:利用3D培养与理化因素刺激等手段提高外泌体产量与活性;使用产量较高的人工合成细胞外囊泡模拟物替代外泌体;以水凝胶与3D打印材料等支架负载外泌体, 以提供稳定的促神经修复环境。Spinal cord injury(SCI)can lead to severe sensory and motor dysfunction pathologically characterized by direct axonal rupture,nerve cell necrosis and apoptosis.Traditional interventions,such as drug therapy and cell therapy,have limited efficacy associated with a poor prognosis in patients of SCI.In recent years,exosomes have become a new hotspot for spinal cord injury repair for their unique phospholipid properties and nucleic acid and protein inclusions.Exosomes can be produced by various cells with the assistance of molecules related to intracellular vesicle transport,such as endosomal sorting complex proteins,rat sarcoma-associated proteins and lipids.Those exosomes with structural and functional diversity due to the molecular composition of their respective cell sources,can be targeted on different receptor cells and play a key role in inhibiting glial scar formation,reducing inflammation and promoting nerve regeneration and repair.By identifying the target of exosomes derived from mesenchymal stem cells,neural stem cells,and Schwann cells for spinal cord injury repair,individualized therapy becomes possible based on the specific cell and molecular background of the patient's injury type,thus enhancing the effectiveness and safety of therapy.However,clinical use of exosomes still has limitations because of its rapid clearance,unstable therapeutic concentration in injured site and lack of separation and purification methods that both satisfies the separation efficiency and specificity.On the basis of the separation and purification methods summarized by International Society of Extracellular Vesicles,efforts are made by using 3D culture and stimulation of physical and chemical factors to improve exosome production and activity,using synthetic extracellular vesicle mimics with higher yield to replace exosomes and loading exosomes with scaffolds such as hydrogels and 3D printing materials to provide a stable environment for promoting nerve repair.

关 键 词：脊髓损伤 外泌体 脊髓再生 

分 类 号：R651.2[医药卫生—外科学]