人脐带间充质干细胞通过外泌体miRNA预防骨髓干细胞移植后aGVHD的效应和机制研究  

Human Umbilical Cord-Derived Mesenchymal Stem Cells Prevent Acute Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation Via Exosome-Mediated MicroRNA and Its Mecha-nism

作　　者：骆宜茗 钟佳颖[3] 简欣怡 张礼翼 张黎 丁毅 马云瀚[3] 陈映宇 林清如 齐忠权 LUO Yi-Ming;ZHONG Jia-Ying;JIAN Xi-Yi;ZHANG Li-Yi;ZHANG Li;DING Yi;MA Yun-Han;CHEN Ying-Yu;LIN Qing-Ru;QI Zhong-Quan(The School of Clinical Medicine,Fiujiaon Medical University,Fiuzhou 350108,Fiujian Province,China;Department of Hematology,The First Affiliated Hospital of Xiamen University,Institute of Hematology,Medical College,Xiamen University,Xiamen 361003,Fujian Province,China;Organ Transplantation Institute,Medical College,Xiamen University,Xiamen 361102,Fiujian Province,China;Graduate College of Fujian Medical University,Fuzhou 350108,Fujian Province,China;Deparment of Pathology,The First Affiliated Hospital of Xiamen University,Xiamen 361003,Fujian Province,China;Medical College of Guangxi University,Nanning 530004,Giuangxi Province,China)

机构地区：[1]福建医科大学临床医学部,福建福州350108 [2]厦门大学附属第一医院血液科,厦门大学医学院血液病研究所,福建厦门361003 [3]厦门大学医学院器官移植研究所,福建厦门361102 [4]福建医科大学研究生院,福建福州350108 [5]厦门大学附属第一医院病理科,福建厦门361003 [6]广西大学医学院,广西南宁530004

出　　处：《中国实验血液学杂志》2023年第4期1171-1178,共8页Journal of Experimental Hematology

基　　金：国家自然科学基金(81971505);福建省自然基金(2019J01577);科技部国家重点研发计划项目(2018YFA0108304)。

摘　　要：目的:探索脐带间充质干细胞抑制骨髓干细胞移植后GVHD发生的分子机制。方法:通过构建小鼠骨髓干细胞移植后急性移植物抗宿主病(aGVHD)的模型,并将脐带间充质干细胞用于aGVHD小鼠模型中观察其预防效应。同时通过分离脐带间充质干细胞外泌体,观察外泌体对aGVHD小鼠的预防效应。通过对脐带间充质干细胞和外泌体进行miRNA测序、分析和验证,探索脐带间充质干细胞外泌体预防骨髓干细胞移植后aGVHD的分子机制。结果:成功构建了小鼠骨髓干细胞移植后aGVHD模型。与骨髓干细胞移植后aGVHD模型小鼠相比,注射脐带间充质干细胞能够降低移植小鼠aGVHD评分,延长小鼠的生存时间。而脐带间充质干细胞的外泌体注射同样具有降低aGVHD评分,延长移植小鼠生存时间的疗效。高通量测序结果显示,脐带间充质干细胞的外泌体中富含miR-21等miRNA分子,主要影响细胞粘附、细胞RNA降解等信号通路。结论:脐带间充质干细胞能够预防骨髓干细胞移植后aGVHD的发生,该效应可能由脐带间充质干细胞的外泌体中miRNA所介导。Objective:To explore molecular mechanisms by which umbilical cord-derived mesenchymal stem cells suppress the development of GVHD after bone marrow hematopoietic stem cell transplantation.Methods:A mouse model of aGVHD was constructed after bone marrow hematopoietic stem cell transplantation,and the umbilical cord-derived mesenchymal stem cells were cultured,and then injected into the aGVHD mouse model,so as to investigate its prophylactic efficacy.Prophylactic effect of the exosomes isolated from umbilical cord-derived mesenchymal stem cells on aGVHD mice was assessed.Sequencing analysis of miRNA from exosomes was performed.Results:aGVHD model was successfully constructed after hematopoietic stem cell transplantation.By injecting umbilical cord-derived mesenchymal stem cells into the GVHD mouse model,it was found that the treatment significantly prolonged survival time of mice compared to the untreated group.Injection exosomes derived from umbilical cord-derived msenchymal stem cells into the GVHD mouse model significantly prolonged the survival time of mice compared to the untreated group.High-throughput sequencing data showed that microRNA such as miR-21 in exosomes isolated from umbilical cord-derived mesenchymal stem cells,which mainly affected the signaling pathways such as cell adhesion,RNA degradation.Conclusion:The umbilical cord-derived mesenchymal stem cells can prevent the occurence of aGVHD after HSCT,which is mediate by MicroRNA in the exosomes derived from umbilical cord-derived mesenchymal stem cells.

关 键 词：造血干细胞移植 移植物抗宿主病 脐带间充质干细胞 外泌体 微小RNA 

分 类 号：R457.7[医药卫生—治疗学]