负载miRNA间充质干细胞源外泌体改善脊髓损伤的作用机制  

Action mechanism of mesenchymal stem cell-derived exosomes carrying miRNAs in improving spinal cord injury

作　　者：郭佳 任亚锋[2] 李冰[2] 黄靖 尚文雅 杨溢珂 刘慧瑶 Guo Jia;Ren Yafeng;Li Bing;Huang Jing;Shang Wenya;Yang Yike;Liu Huiyao(School of Rehabilitation Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,Henan Province,China;First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,Henan Province,China)

机构地区：[1]河南中医药大学康复医学院,河南省郑州市450046 [2]河南中医药大学第一附属医院,河南省郑州市450000

出　　处：《中国组织工程研究》2025年第36期7827-7838,共12页Chinese Journal of Tissue Engineering Research

基　　金：河南省中医药科学研究专项课题(2021JDZY022,2022JDZY015),项目负责人:任亚锋;河南中医药大学“双一流”创建工程中医学学科项目(HSRP-DFCTCM-2023-1-25),项目负责人:任亚锋。

摘　　要：背景:目前,脊髓损伤给患者和国家医疗服务带来巨大的负担,有关于脊髓损伤预防、治疗和康复已成为医学领域的一个重要课题。因此,在深入了解脊髓损伤潜在分子机制的基础上,探索新的有效治疗策略具有重要意义。目的:综述负载多种miRNA的间充质干细胞源外泌体在改善脊髓损伤功能方面作用机制的研究进展,并基于临床转化现状,对其投入临床使用提出几点思考和展望。方法:由第一作者检索中国知网和PubMed数据库,分别以“间充质干细胞,外泌体,脊髓损伤,miRNA,病理生理学,临床转化,临床试验,良好生产规范”及“mesenchymal stem cells,exosome,spinal cord injury,miRNA,pathophysiology,clinical translation,clinical trial,good manufacturing practice”为中英文检索词检索相关文献。文献类型包括论著和综述,语言种类为英文和中文,最终筛选出72篇文献进行综述分析。结果与结论:(1)文章概述了外泌体的生物特性和其可作为负载miRNA良好载体的优势。由间充质干细胞源外泌体介导的多种miRNA主要通过调节神经再生相关蛋白的表达、抑制RAS同源基因家族成员A、激活环磷腺苷效应元件结合蛋白和信号传导及转录激活蛋白3、调节磷酸酯酶与张力蛋白同源物/程序性细胞死亡因子4通路等多个方面来促进神经元功能的恢复;通过调节内质网到细胞核信号1、干扰素调节因子5的表达、Toll样受体4/核转录因子kB通路、下调相关促炎因子等方面来改善炎症反应;抑制含发芽相关的EVH1域1和磷酸肌醇3激酶调节亚基2来促进血管生成。(2)进一步对比分析发现,miR-216-5p,miR-145-5p及miR-146b均通过调节相关通路来改善炎症反应,将这些miRNA联合运用可能会产生更显著效果;缺氧预处理可能是一种增加外泌体治疗效果的预处理方法。(3)目前尚无将间充质干细胞源外泌体应用于脊髓损伤的临床试验,这与其投入临床�BACKGROUND:Currently,spinal cord injury imposes a huge psychological and economic burden on patients and the National Health Service.The prevention,treatment,and rehabilitation of spinal cord injury have become an important topic in the field of medicine.Therefore,it is important to explore new effective therapeutic strategies based on an in-depth understanding of the underlying molecular mechanisms of spinal cord injury.OBJECTIVE:To review the research progress on the mechanism of action of mesenchymal stem cell-derived exosomes loaded with various miRNAs in improving the function of spinal cord injury,and based on the current status of clinical translation,to put forward a few thoughts and outlooks on their clinical use.METHODS:The first author searched CNKI and PubMed databases using“mesenchymal stem cells,exosomes,spinal cord injury,miRNA,pathophysiology,clinical translation,clinical trials,good manufacturing practice”as Chinese and English search terms.The types of literature included treatises and reviews,and the language types were English and Chinese.Finally,72 papers were screened and analyzed.RESULTS AND CONCLUSION:(1)This article outlines the biological properties of exosomes and the advantages that they can serve as good vectors for loading miRNAs.A variety of miRNAs mediated by mesenchymal stem cell-derived exosomes mainly promote the recovery of neuronal function by regulating the expression of nerve regeneration-associated proteins,repressing RAS homologous gene family member A,activating cyclophosphoadenosine effector-binding proteins,and signaling and transcriptional activation proteins 3,and regulating phosphoinositide and tensin homologue/programmed cell death factor 4 pathways.Inflammatory responses were improved by regulating endoplasmic reticulum-to-nucleus signaling 1,expression of interferon regulatory factor 5,Toll-like receptor 4/nuclear factor-kappa B pathway,and down-regulating related pro-inflammatory factors.Angiogenesis was promoted by inhibition of germination-associated domain

关 键 词：脊髓损伤 间充质干细胞 外泌体 MIRNA 病理生理学 临床转化 临床试验 良好生产规范 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R651.2