人脐带间充质干细胞的体外免疫调节特性  

Immunomodulatory characteristics of human umbilical cord mesenchymal stem cells in vitro

作　　者：刘梦婷 饶巍 韩兵 肖翠红 武栋成 Liu Mengting;Rao Wei;Han Bing;Xiao Cuihong;Wu Dongcheng(R&D Center,Wuhan Hamilton Biotechnology Co.,Ltd.,Wuhan 430075,Hubei Province,China;School of Basic Medical Science,Wuhan University,Wuhan 430071,Hubei Province,China)

机构地区：[1]武汉汉密顿生物科技股份有限公司研发中心,湖北省武汉市430075 [2]武汉大学基础医学院,湖北省武汉市430071

出　　处：《中国组织工程研究》2020年第7期1063-1068,共6页Chinese Journal of Tissue Engineering Research

基　　金：武汉市第十一批3551光谷人才计划(武新管[2018]48号)，项目参与人：武栋成~~

摘　　要：背景:人脐带间充质干细胞被应用于治疗多种疾病,包括与免疫相关疾病的临床应用研究。深入研究人脐带间充质干细胞免疫调节特性及其作用途径,是其临床应用的基础。目的:探讨人脐带间充质干细胞的免疫调节特性及作用途径。方法:人脐带间充质干细胞与荧光染料CFSE标记的人外周血单个核细胞直接共培养(二者比例为1∶5,1∶10,1∶20),或在Transwell非接触体系中间接共培养(二者比例为1∶5),流式细胞术检测植物血凝素刺激的外周血单个核细胞增殖情况,Th1、Th17及Treg淋巴细胞亚群的比例;ELISA检测炎症因子肿瘤坏死因子α及干扰素γ水平。结果与结论:①直接接触共培养时,人脐带间充质干细胞对植物血凝素刺激的外周血单个核细胞增殖呈显著的剂量依赖性抑制;采用非接触培养体系,外周血单个核细胞的增殖未受明显抑制;②人脐带间充质干细胞共培养显著抑制炎性淋巴细胞Th1、Th17亚群的比例,升高抑制性淋巴细胞Treg的比例;③人脐带间充质干细胞共培养显著性抑制外周血单个核细胞的肿瘤坏死因子α及干扰素γ分泌水平;④结果显示,人脐带间充质干细胞通过细胞间相互接触而对免疫细胞的增殖、分化及其炎症因子的产生发挥抑制性调节作用。BACKGROUND:Human umbilical cord mesenchymal stem cells(hUC-MSCs)have been drawing a great attention due to their potential therapeutic effect in a variety of diseases,including immune-mediated diseases.Further characterization of the immunomodulatory properties and action pathways of hUC-MSCs is necessary to ensure their safety and effectiveness in clinical application.OBJECTIVE:To investigate the immunomodulatory properties of hUC-MSCs.METHODS:hUC-MSCs were directly co-cultured with CFSE-labeled peripheral blood mononuclear cells(PBMCs)at the ratio of 1:5,1:10,and 1:20,or indirectly co-cultured with CFSE-labeled PBMCs at the ratio of 1:5 via the Transwell co-culture system.Phytohemagglutininstimulated PBMC proliferation and the percentages of Th1,Th17 and Treg subgroups in the CD4^+T cells were determined by flow cytometry.The levels of tumor necrosis factor α and interferonγwere determined by ELISA.RESULTS AND CONCLUSION:After direct co-culture,hUC-MSCs significantly inhibited the phytohemagglutinin-stimulated PBMCs proliferation in a dose-dependent manner,whereas the inhibitory effect disappeared in the Transwell co-culture system.A significant decrease of Th1,Th17 cells and an increase of Treg cells were detected in the PBMCs co-cultured with hUC-MSCs compared to the PBMCs cultured alone.Furthermore,hUC-MSCs co-culture significantly reduced tumor necrosis factorαand interferonγlevels in the PBMCs.These findings indicate that cell-to-cell contact is essential for hUC-MSCs to inhibit the proliferation,differentiation and inflammatory factor secretion of immune cells.

关 键 词：人脐带间充质干细胞 免疫调节 免疫抑制 炎症抑制 淋巴细胞增殖 淋巴细胞亚群 

分 类 号：R459.9[医药卫生—治疗学] R394.2[医药卫生—临床医学]