骨髓MSCs对GVHD模型大鼠的免疫调节作用  

Immunoregulatory effects of bone marrow MSCs in GVHD model rats

作　　者：杨兴肖[1] 单保恩[1] 马鸣[2] 张会超[2] 刘丽华[1] 艾军[1] 赵连梅[1] 张小芳[1] 

机构地区：[1]河北医科大学第四医院科研中心,石家庄050011 [2]河北医科大学第四医院检验科,石家庄050011

出　　处：《免疫学杂志》2011年第4期301-306,327,共7页Immunological Journal

基　　金：河北省高校强势特色学科(200552)

摘　　要：目的探讨骨髓源间充质干细胞(mesenchymal stem cells,MSCs)对移植物抗宿主病(graft versus host disease,GVHD)模型大鼠的免疫调节作用。方法从SD大鼠骨髓中分离培养MSCs。通过给放射线照射过的Wistar大鼠进行干细胞和单个核细胞(mononuclear cell,MNC)共同移植,建立大鼠GVHD模型,对其进行异基因骨髓移植的同时,共输注不同数量的供者源性的MSCs,观察受鼠的一般表现、生存期及病理损伤的变化;利用细胞免疫化学检测各实验组大鼠外周血MNC中Foxp3+细胞比例的变化,应用ELISA方法检测实验各组大鼠外周血血清中细胞因子IFN-γ、IL-4的变化,诱导各组受鼠脾脏MNC为CTL,并用MTT法检测各组受鼠CTL的杀伤活性。结果异基因骨髓移植时,共输注供鼠MSCs能够明显降低GVHD的发生率,并减轻其病理损伤,延长生存时间;共输注MSCs受鼠血清中IFN-γ水平明显减低而IL-4水平明显增加(P<0.05),与GVHD组大鼠相比,共输注MSCs的各组大鼠外周血中Foxp3+细胞比例明显增加(P<0.05),而CTL杀伤活性明显减弱。结论 MSCs能够通过免疫调节作用抑制GVHD的发生,降低其严重程度,并延长受鼠生存时间。This study aimed to investigate the immunoregulatory effects of mesenchymal stem cells（MSCs） on graft versus host disease（GVHD） after allogeneic bone marrow transplantation（allo-BMT）.MSCs from bone marrow cells of SD rats were isolated and cultured in vitro;allogeneic BMT model from SD rats to radiated Wistar rats was established,then MSCs were cotransplanted with bone marrow cells at different ratios,and the suppressive effects of MSCs on GVHD were studied by general appearance,lifespan,and pathological changes of target organs.Percentage of Foxp3＋ cells in peripheral blood mononuclear cells were observed by cell immunology chemical method;effects of MSCs on concentration of IFN-γ and IL-4 in serum of peripheral blood were determined by ELISA assay;effect of MSCs on cytotoxicity of CTL was investigated by MTT method after spleen mononuclearcells of recipient rats were induced.We found that cotransplantation with mesenchymal stem cells in rats after allogeneic bone marrow transplantation decreased the incidence rate of GVHD obviously,alleviated pathological damage,and prolonged survival time.In cotransplantation groups,the level of IFN-γ was decreased,but the level of IL-4 increased markedly in serum of peripheral blood（P 0.01） in a dose-dependent manner.Compared with GVHD group,percentage of Foxp3＋ cells in peripheral blood mononuclear cell increased obviously（P 0.05） and cytotoxicity of CTL was impaired in cotransplantation groups.We concluded that MSCs may inhibit the development of GVHD,reduce the severity of pathology impairment,and prolong survival time of recipient rats through the immunoregulatory effects.

关 键 词：大鼠 间充质干细胞 移植物抗宿主病 免疫调节 

分 类 号：R392.12[医药卫生—免疫学]