间充质干细胞分泌组发挥作用的分子机制  

Molecular mechanisms underlying role of mesenchymal stem cell secretome

作　　者：李佳林 张耀东[1,2,3,4,5] 娄艳茹[1,2,3,4,5] 于洋 杨蕊 Li Jialin;Zhang Yaodong;Lou Yanru;Yu Yang;Yang Rui(State Key Laboratory of Female Fertility Promotion,Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Peking University Third Hospital,Beijing 100191,China;National Clinical Research Center for Obstetrics and Gynecology(Peking University Third Hospital),Beijing 100191,China;Key Laboratory of Assisted Reproduction(Peking University),Ministry of Education,Beijing 100191,China;Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology,Beijing 100191,China;National Clinical Key Specialty Construction Program,P.R.China(2023),Beijing 100191,China)

机构地区：[1]北京大学第三医院,妇产科,生殖医学中心,女性生育力促进全国重点实验室,北京市100191 [2]国家妇产疾病临床医学研究中心(北京大学第三医院),北京市100191 [3]辅助生殖教育部重点实验室(北京大学),北京市100191 [4]生殖内分泌与辅助生殖技术北京市重点实验室,北京市100191 [5]国家临床重点专科建设项目(2023)专项资金,北京市100191

出　　处：《中国组织工程研究》2025年第7期1512-1522,共11页Chinese Journal of Tissue Engineering Research

基　　金：国家重点研发计划课题(2021YFC2700605),项目负责人:杨蕊;国家自然科学基金项目(82171632),项目负责人:杨蕊;北京大学临床医学+X青年专项(PKU2023LCXQ045),项目负责人:杨蕊。

摘　　要：背景:大量研究证实间充质干细胞分泌组的治疗有效性与间充质干细胞相当,但对于其发挥作用的机制尚不清楚。目的:总结近年来关于间充质干细胞分泌组的研究进展,探究其发挥治疗作用的分子机制,分析目前面临的问题并展望未来发展方向。方法:以“exosomes,mesenchymal stem cells secrete,extracellular vesicles,mesenchymal stem cells,mechanism”为英文检索词检索PubMed数据库相关文献,排除与文章研究目的无关及重复性文章,同时结合文献追踪的方法,最终纳入符合要求的109篇文献进行综述。结果与结论:(1)间充质干细胞分泌组通过递送遗传物质、免疫调节因子和生长因子等到靶细胞,通过激活靶细胞抗凋亡和促生存途径,调节血管生成,调节纤维化以及调节免疫微环境,促进组织修复和再生。(2)间充质干细胞分泌组在疾病治疗方面的潜力也得到证实,大量研究结果表明,间充质干细胞分泌组可以作为炎症疾病和退行性疾病的新型无细胞替代治疗方法。(3)近年来,经过工程化改造间充质干细胞分泌组发挥的治疗作用更加高效,但是由于间充质干细胞分泌组的异质性以及成分的复杂性,其发挥治疗作用的具体机制尚不清楚。(4)目前,仍需要进一步研究来明确间充质干细胞分泌组发挥治疗作用的关键靶点,并且未来应结合工程化和基因工程技术等,研发出具有创新性的特异型、增强型间充质干细胞分泌组。BACKGROUND:A large number of studies have confirmed that the therapeutic effectiveness of mesenchymal stem cell secretome is comparable to that of mesenchymal stem cells,but the mechanism of its action is still unclear.OBJECTIVE:To summarize the research progress of mesenchymal stem cell secretome in recent years,to investigate the molecular mechanism of its therapeutic effect,to analyze the current problems and to look forward to the future development.METHODS:The terms “exosomes,mesenchymal stem cells secrete,extracellular vesicles,mesenchymal stem cells,mechanism” were used as English search terms in the PubMed database.Articles that were not related to the research purpose of the article and duplicated articles were excluded.At the same time,we combined the method of literature tracking.Finally,109 articles that met the criteria were incuded for the review.RESULTS AND CONCLUSION:(1) The mesenchymal stem cell secretome promotes tissue repair and regeneration through delivering genetic material,immunomodulatory factors,growth factors,etc.to target cells,by activating anti-apoptotic,regulating angiogenesis,modulating fibrosis and pro-survival pathways in target cells.(2) The potential of mesenchymal stem cell secretome in disease therapy has also been confirmed.Numerous research results have shown that mesenchymal stem cell secretome can be used as a new cell-free treatment for inflammatory and degenerative diseases.(3) Mesenchymal stem cell secretome has been engineered to have more efficient therapeutic effects in recent years.However,due to the heterogeneity of the mesenchymal stem cell secretome and the complexity of its components,the exact mechanism of its therapeutic effect is still unclear.(4) At present,further research is needed to identify the key targets of mesenchymal stem cell secretome,and innovative specific and enhanced mesenchymal stem cell secretome should be developed by combining with engineering and genetic engineering technologies in the future.

关 键 词：间充质干细胞 外泌体 细胞外囊泡 间充质干细胞分泌组 免疫调节 组织修复 再生医学 分子机制 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R364