间充质干细胞诱导的CD8α^+ Jagged2^(high) CD11b^(high)调节性树突状细胞防治小鼠aGVHD  

Mesenchymal stem cell-induced CD8α^+ Jagged2^(high) CD11b^(high) regulatory dendritic cells prevent and treat mouse a GVHD

作　　者：童嘉琦[1,2] 吴萍[1,2] 黄欣[2] 赖沛龙[2] 耿素霞[2] 翁建宇[2] 杜欣[2] 

机构地区：[1]南方医科大学,广东广州510515 [2]广东省人民医院血液科广东省医学科学院,广东广州510080

出　　处：《中国病理生理杂志》2015年第5期882-887,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30972790;No.81270648;No.81370665;No.81300446);广东省自然科学基金资助项目(No.S2012010009560);广东省科技计划(No.2013B021800186;No.2013B021800201);广州市科技计划(No.201400000003-4;No.201400000003-1)

摘　　要：目的:观察间充质干细胞诱导的CD8α+Jagged2highCD11bhigh调节性树突状细胞(MSC-DCregs),对小鼠急性移植物抗宿主病(a GVHD)的影响。方法:体外诱导MSC-DCregs。以C57BL/6(H-2b)小鼠为供鼠、接受清髓性全身照射(TBI)预处理的BALB/c(H-2d)小鼠为受鼠进行移植。分为以下5组:为正常对照组;TBI组;移植组:移植物为1×107骨髓细胞(BMCs);a GVHD组:移植物为1×107BMCs+1×107脾细胞(Sp Cs);MSC-DCregs组:移植物为1×107BMCs+1×107Sp Cs+1×106MSC-DCregs。监测植入情况、H2-Kb嵌合率、a GVHD评分、生存和病理学改变。结果:处理1 0 d后所有小鼠造血恢复,30 d后嵌合率检测转为供鼠型。a GVHD组和MSC-DCregs组中位生存期分别为27 d和33 d,MSC-DCregs组生存期较a GVHD组延长(P<0.01),临床评分比a GVHD组低(P<0.01),33 d的皮肤、肝脏病理学改变均优于a GVHD组。结论:MSC-DCregs具有防治a GVHD的作用,其相关作用机理待进一步研究。AIM：To investigate the role of mesenchymal stem cell-induced regulatory dendritic cells （ MSC-DCregs） in mouse acute graft-versus-host disease（ aGVHD） model.METHODS： Bone marrow cells from BALB/c （ H-2 d ） mice were isolated and were induced to differentiate into DCs.The DCs were selected by flow cytometry, and after 10 d co-culture with MSCs, they were induced to be MSC-DCregs.Male 8-week-old C57BL/6 （H-2b） mice were used as do-nor mice.The female 8-week-old BALB/c （H-2d） mice, who had received 100 cm source-skin distance, 30 cm ×30 cm radiation field, 700 cGy total body irradiation （TBI） pretreatment were used as recipient mice.The recipients were divided into 5 groups：control group, TBI group （ injected with medium only） , bone marrow transplantation group （ injected with 1 ×107 bone marrow cells）, aGVHD group （injected with 1 ×107 bone marrow cells and 1 ×107 spleen cells）, and MSC-DCregs group （injected with 1 ×107 bone marrow cells, 1 ×107 spleen cells and 1 ×106 MSC-DCregs）.The white blood cell count, recipients’ chimerism, clinical evaluation of aGVHD, survival analysis and pathological changes were deter-mined.RESULTS：Hematopoieic recovery was seen at 10 d after transplantation.The recipients’ chimerism was parallel to the donors’ at 30 d.The median survival time of the mice in aGVHD group and MSC-DCregs group was 27 d and 33 d, and the survival rates at 30 d were 20% and 100% （P〈0.01）, respectively.The clinical scores of the mice in MSC-DCregs group were lower than those in aGVHD group （ P〈0.01） .Moreover, the pathological changes in the skin and liver of the mice in MSC-DCregs group were less serious than those in aGVHD group.CONCLUSION： The MSC-DCregs in-duce an aGVHD tolerance in vivo, and further research of its mechanism is still in great necessary.

关 键 词：间充质干细胞 调节性树突状细胞 急性移植物抗宿主病 

分 类 号：R392.12[医药卫生—免疫学]