基于细胞外囊泡的联合疗法治疗坐骨神经损伤的研究进展

Research progress on extracellular vesicle-based combination therapy for the treatment of sciatic nerve injury

关键词:  生物材料  联合治疗  药物输送  细胞外囊泡  功能恢复  外界刺激  坐骨神经损伤  组织工程

Key words:  biomaterials  combination therapy  drug delivery  extracellular vesicles  functional restoration  external stimuli  sciatic nerve injury  Tissue engineering

摘要:

坐骨神经损伤是对神经系统的严重损害,属于周围神经病变的一种,可导致持续的神经功能障碍。目前可用的治疗方法包括手术治疗、药物和康复牵引。然而,这些技术都不能显著逆转神经功能缺损。最近,不同细胞来源的细胞外囊泡已被应用于不同的坐骨神经损伤模型,从而产生了新的治疗坐骨神经损伤的方法。然而,单一的细胞外囊泡疗法同样存在一些明显的缺点,例如,人的肌肉组织体积大,坐骨神经是体内最大的神经,严重的坐骨神经损伤往往病灶大且复杂,细胞外囊泡是否可以在肌肉组织中达到同样的治疗效果不得而知。因此,本文综述了利用细胞外囊泡为基础的技术治疗坐骨神经损伤的最新组合策略,包括细胞外囊泡与生物材料、药物与外界刺激的组合,这些组合有利于细胞外囊泡的靶向能力以及与细胞外囊泡的组合效应。我们还强调了与这些基于细胞外囊泡的联合策略在坐骨损伤治疗中的临床转化相关的问题。

Abstract:

Sciatic nerve injury is a severe insult to the nervous system that causes persisting neurological deficits,and is a type of peripheral neuropathy that can lead to persistent neurological dysfunction. The currently available treatments involve surgery, medications, and rehabilitative traction. However, none of these techniques can markedly reverse neurological deficits. Recently, extracellular vesicles from various cell sources have been applied to different models of sciatic nerve injury,thereby generating new cell-free therapies for the treatment of sciatic nerve injury. However, the use of extracellular vesicles alone is still associated with some notable shortcomings, such as, the size of human muscle tissue is large, the sciatic nerve is the largest nerve in the body, severe sciatic nerve injury is often large and complex, and it is unknown whether extracellular vesicles can achieve the same therapeutic effect in muscle tissue. Therefore, this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for sciatic nerve injury, including the combination of extracellular vesicles and biomaterials, drugs and external stimuli, which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles. We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of sciatic nerve injury.