CAJ | 학술논문

目的：观察间充质干细胞诱导的CD8α＋Jagged2high CD11bhigh调节性树突状细胞（MSC-DCregs），对小鼠急性移植物抗宿主病（aGVHD）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）；aGVHD组：移植物为1×107 BMCs＋1×107脾细胞（ SpCs）；MSC-DCregs组：移植物为1×107 BMCs＋1×107 SpCs＋1×106 MSC-DCregs。监测植入情况、H2-Kb嵌合率、aGVHD评分、生存和病理学改变。结果：处理10 d后所有小鼠造血恢复，30 d后嵌合率检测转为供鼠型。 aGVHD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aGVHD组延长（P＜0.01），临床评分比aGVHD组低（P＜0.01），33 d的皮肤、肝脏病理学改变均优于aGVHD组。结论： MSC-DCregs具有防治aGVHD的作用，其相关作用机理待进一步研究。
목적：관찰간충질간세포유도적CD8α＋Jagged2high CD11bhigh조절성수돌상세포（MSC-DCregs），대소서급성이식물항숙주병（aGVHD）적영향。방법：체외유도MSC-DCregs。이C57BL／6（H-2b）소서위공서、접수청수성전신조사（TBI）예처리적BALB／c （H-2d）소서위수서진행이식。분위이하5조：위정상대조조；TBI조；이식조：이식물위1×107골수세포（ BMCs）；aGVHD조：이식물위1×107 BMCs＋1×107비세포（ SpCs）；MSC-DCregs조：이식물위1×107 BMCs＋1×107 SpCs＋1×106 MSC-DCregs。감측식입정황、H2-Kb감합솔、aGVHD평분、생존화병이학개변。결과：처리10 d후소유소서조혈회복，30 d후감합솔검측전위공서형。 aGVHD조화MSC-DCregs조중위생존기분별위27 d화33 d，MSC-DCregs조생존기교aGVHD조연장（P＜0.01），림상평분비aGVHD조저（P＜0.01），33 d적피부、간장병이학개변균우우aGVHD조。결론： MSC-DCregs구유방치aGVHD적작용，기상관작용궤리대진일보연구。
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.