间充质干细胞及其外泌体在外周神经损伤修复中的研究进展与物理调控展望

Research progress and physical regulation prospects of mesenchymal stem cells and their exosomes in peripheral nerve injury repair

  • 摘要: 外周神经损伤常导致长期运动、感觉及疼痛障碍,传统显微修复和自体神经移植仅能恢复功能,难以应对长段缺损与复杂损伤场景。尽管间充质干细胞移植在早期研究中展现出神经修复潜力,但其临床转化面临致瘤风险、免疫排斥、细胞存活率低及标准化困难等挑战。研究表明,MSC的治疗效应主要通过旁分泌机制而非细胞替代实现,这一发现推动了无细胞疗法的发展。MSC来源的外泌体富含miR‑21、miR‑146a、miR‑126 等关键miRNA,可通过激活PI3K/Akt/mTOR信号通路促进轴突再生,抑制NF‑κB通路减轻神经炎症,并诱导巨噬细胞M2 极化改善免疫微环境,已成为PNI生物治疗最活跃的研究方向之一。另一方面,以电刺激、超声、光、生物电磁场为代表的物理治疗正在从“康复手段”演变为直接调控神经再生微环境和干细胞行为的“能量药物”,并可与生物材料协同构建多功能调控平台。本文在系统梳理近年来MSC及MSC‑Exos 促进PNI修复的细胞与分子机制、工程化策略和转化进展的基础上,重点评述其与生物材料及外源物理刺激的协同效应,阐明从细胞替代疗法向无细胞外泌体疗法转变的科学依据,并据此展望太赫兹等新型电磁波段在MSC预处理与微环境精细调控中的潜在应用。

     

    Abstract: Peripheral nerve injury (PNI) often leads to long‑term motor, sensory and pain disorders. Traditional microscopic repair and autologous nerve transplantation can partially restore function and make it difficult to cope with long‑segment defects and complex injury scenarios. Although mesenchymal stem cell (MSC) transplantation has shown neurorepair potential in early studies, its clinical translation faces challenges such as tumorigenic risk, immune rejection, low cell survival rate, and standardization difficulties. Studies have demonstrated that the therapeutic effects of MSCs are mainly achieved through paracrine mechanisms rather than cell replacement, a finding that has promoted the development of cell‑free therapies. MSC‑derived exosomes (MSC‑Exos) are rich in key miRNAs such as miR‑21, miR‑146a, and miR‑126. They can promote axonal regeneration by activating the PI3K/Akt/mTOR signaling pathway, inhibit the NF‑κB pathway to reduce neuroinflammation, and induce M2 polarization of macrophages to improve the immune microenvironment. Thus, MSC‑Exos have become one of the most active research directions in biological therapy for peripheral nerve injury (PNI). On the other hand, physical therapies represented by electrical stimulation, ultrasound, light, and bioelectromagnetic fields are evolving from "rehabilitation methods" to "energy drugs" that directly regulate the neuroregenerative microenvironment and stem cell behavior, and can collaborate with biomaterials to construct multifunctional regulatory platforms. Based on a systematic review of recent advances in the cellular and molecular mechanisms, engineering strategies, and translational progress of MSCs and MSC‑Exos in promoting PNI repair, this article focuses on reviewing their synergistic effects with biomaterials and exogenous physical stimuli (electricity, magnetism, ultrasound, etc.), clarifies the scientific basis for the shift from cell replacement therapy to cell‑free exosome therapy, and accordingly prospects the potential application of new electromagnetic wavebands such as terahertz (THz) in MSC preconditioning and fine regulation of the microenvironment.

     

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