间充质干细胞及其衍生细胞外囊泡靶向巨噬细胞干预自身免疫性疾病  

Mesenchymal stem cells and their derived extracellular vesicles target macrophages to intervene in autoimmune diseases

作　　者：姚兰宣 王雪菲 刘洋 杨雨佳 赵怡 齐芳芳 李颖辉[2,4] Yao Lanxuan;Wang Xuefei;Liu Yang;Yang Yujia;Zhao Yi;Qi Fangfang;Li Yinghui(School of Stomatology,Hebei Medical University,Shijiazhuang 050000,Hebei Province,China;Hebei Key Laboratory of Stomatology,Shijiazhuang 050000,Hebei Province,China;Department of Operative Dentistry and Endodontics,Stomatological Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei Province,China;Department of Orthodontics,Stomatological Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei Province,China)

机构地区：[1]河北医科大学口腔医学院,河北省石家庄市050000 [2]河北省口腔医学重点实验室,河北省石家庄市050000 [3]河北医科大学口腔医院牙体牙髓科,河北省石家庄市050000 [4]河北医科大学口腔医院正畸科,河北省石家庄市050000

出　　处：《中国组织工程研究》2025年第31期6772-6781,共10页Chinese Journal of Tissue Engineering Research

基　　金：河北医科大学2023年大学生创新性实验计划立项项目(USIP2023110),指导老师:李颖辉;河北省医学课题研究计划(20221446),项目负责人:齐芳芳。

摘　　要：背景:巨噬细胞是机体固有免疫的重要组成部分,当机体内环境发生改变时巨噬细胞可以产生不同的极化表型,并发挥相应的炎性免疫作用。间充质干细胞能够分泌较多数量的细胞外囊泡到机体内环境中,具有细胞间信号传导及免疫调节功能。研究表明,间充质干细胞及间充质干细胞来源细胞外囊泡可以影响巨噬细胞M1/M2极化平衡,从而治疗机体免疫炎症性疾病。目的:探讨间充质干细胞及其来源细胞外囊泡通过调节巨噬细胞极化来干预自身免疫性疾病的信号机制,以及工程化细胞外囊泡在此领域的相关研究进展。方法:第一作者检索PubMed、中国知网等数据库自建库到2024年6月发表的相关文献,以“间充质干细胞,细胞外囊泡,外泌体,凋亡小体,凋亡囊泡,巨噬细胞极化,M1极化,M2极化,自身免疫性疾病,多发性硬化,类风湿性关节炎,系统性红斑狼疮,1型糖尿病,炎症性肠病,自身免疫性泪腺炎,工程化细胞外囊泡,工程化外泌体,药物递送”为中文检索词;以“macrophage polarization,M1 macrophage,M2 macrophage,autoimmune disease,type 1 diabetes,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,autoimmune dacryadenitis,inflammatory bowel disease,mesenchymal stem cells,extracellular vesicles,engineered extracellular vesicles,engineering exosomes,drug delivery”为英文检索词,阅读每篇文献的文题、摘要进行初筛,最终筛选出70篇文献进行归纳分析。结果与结论:①间充质干细胞可以通过释放或间接作用于功能性蛋白来调节M1/M2极化;②间充质干细胞可以通过作用于炎症小体调控巨噬细胞M2极化;③间充质干细胞可以与常用药物组合以增强药物疗效;④间充质干细胞受到炎性刺激后可以调控细胞外囊泡的释放影响巨噬细胞极化;⑤间充质干细胞来源细胞外囊泡可以通过PTEN、NOTCH、核因子κB、Toll样受体、PI3K/AKT等通路靶向巨噬细胞�BACKGROUND:Macrophages are an important part of innate immunity.When the internal environment of the body changes,macrophages can produce different polarization phenotypes and play the corresponding inflammatory immune function.Mesenchymal stem cells can secrete a large number of extracellular vesicles into the internal environment of the body,which have the functions of intercellular signaling and immune regulation.Studies have shown that mesenchymal stem cells and mesenchymal stem cells-extracellular vesicles can affect the M1/M2 polarization balance of macrophages so as to treat immune inflammatory diseases.OBJECTIVE:To explore the signaling mechanism of how mesenchymal stem cells and their extracellular vesicles interfere with autoimmune diseases by regulating the polarization of macrophages,as well as the related research progress of engineered extracellular vesicles in this field.METHODS:The first author searched the relevant literature published in PubMed,CNKI and other databases until June 2024.Chinese search terms were“mesenchymal stem cells,extracellular vesicles,exosomes,apoptotic bodies,apoptotic vesicles,macrophage polarization,M1 polarization,M2 polarization,autoimmune diseases,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,type 1 diabetes mellitus,inflammatory bowel disease,autoimmune dacryadenitis,engineered extracellular vesicles,engineering exosomes,drug delivery.”English search terms were“macrophage polarization,M1 macrophage,M2 macrophage,autoimmune disease,type 1 diabetes,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,autoimmune dacryadenitis,inflammatory bowel disease,mesenchymal stem cells,extracellular vesicles,engineered extracellular vesicles,engineering exosomes,drug delivery.”The title and abstract of each paper were read and initially screened.Finally,70 articles were selected for induction and analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cells can regulate M1/M2 polarization by releasing or indirectly acting on functional pro

关 键 词：间充质干细胞 细胞外囊泡 外泌体 巨噬细胞极化 M1/M2极化 自身免疫性疾病 工程化细胞外囊泡 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] Q257[生物学—细胞生物学]