异基因清髓性与非清髓性造血干细胞移植治疗狼疮鼠的疗效比较

Comparison between both nonablative and ablative stem cell transplantation to treat lupus murine

目的 比较用异基因清髓性干细胞移植 (Allo SCT)和非清髓性干细胞移植 (NST)方法治疗狼疮鼠的有效性及安全性。方法 NST组 2 2只BXSB鼠用fludarabine +环磷酰胺 (CTX)作预处理。Allo SCT组 2 2只BXSB小鼠用马利兰 +CTX作预处理 ,预处理后受者输入经粒细胞集落刺激因子 (G CSF)动员后的供者 (C5 7BL/ 6 )的外周血干细胞 ,用环孢素A(CsA)、甲氨蝶呤 (MTX)预防移植物抗宿主病 (GVHD) ,G CSF促进移植后的造血和免疫重建 ,流式细胞仪检测供者Sca 1+ 含量及移植后受者T淋巴细胞亚群 (CD3-CD5 + 、CD3+ CD5 + )的变化 ,甲基纤维素半固体培养法培养供者的粒 巨噬细胞集落形成单位 (GM CFU) ,PCR法对移植后BXSB鼠嵌合状态进行分析 ,直接免疫荧光法和光镜检测移植前后受者的肾病理变化。结果 G CSF动员后不同时间两组供者外周血单个核细胞 (MNC)、CD+ 34、GM CFU数差异无显普性 (P均 >0 0 5 ) ,G CSF动员后第 7天两组供者MNC、CD34+ 、GM CFU数达最佳水平 ,NST组白细胞下降最低值分别为 (0 6± 0 2 )× 10 9/L ,高于Allo SCT组的 (0 2± 0 1)× 10 9/L (P <0 0 5 ) ,白细胞上升至 1 0× 10 9/L的时间在NST组为 (17 5±6 3)d ,比Allo SCT组明显缩短 (P <0 0 5 ) ,尿蛋白从 转为 +或 -、抗dsDNA抗体滴?

Objective To compare effectiveness and safeness of nonablative stem cell transplantation (NST) and ablative stem cell transplantation (allogenic stem cell transplantation,Allo SCT) to lupus murine (BXSB).Methods Condition regimen of NST group ( n =22) was fludarabine and CTX,while myleran and CTX was condition regimen of Allo SCT group ( n =22).Peripheral blood stem cells of donors (C57B/6) after mobilization with G CSF were infused into recipients (BXSB) after the treatment with condition regimen.GVHD of the two group was prevented with CSA and MTX.Hematopoietic and immune reconstitution of both groups were promoted with G SCF.Scal + of donors and subsets of T cells (CD3 -CD5 +,CD3 +CD5 +) of recipients were measured by flow cytometry.Colonies of GM CFU of donors′stem cells were done by semisolid methylcellulose.Recipients′mixed and complete chimerisms were analysed with PCR,and recipients′kidney pathological changes were measured with direct immunofluorescence and optical microscope after transplantation.Results The number of MNC,Sca 1 + and GM CFU of the two groupsatfer mobilizated by G CSF was no statistically significant difference (all P >0 05).Optimal number of MNC,Sca 1 + and GM CFU appeared at day 7 after mobilization.The down rgeulated lowest value of WBC in NST group was(0 6±0 2)×10 9/L ( P <0 05) and higher than that of Allo SCT group (0 2±0 1)×10 9/L ( P <0 05).The durition of WBC up regulation from the lowest value to 1 0×10 9/L was (17 5±6 3) days in NST group was shorter than that of Allo SCT group ( P <0 05).There was no statistically significant difference in changes of uric protein,anti ds DNA and kidney pathology between both groups ( P >0 05).Incidence of GVHD (only grade I was seen) also had no difference between both groups.Early immune reconstitution began to recover after 8 weeks of transplantation in NST group,but early immune reconstitution was not found in Allo SCT group.Incidences of complications of bleeding,loss in weight,neumonia and mortality related to transplantation were lower in NST group than in Allo SCT group (All P <0 05).Recipients′mixed or complete chimerism was observed after 30 days or atfer 45 days of Allo SCT,respectively.Conclusion NST and Allo SCT may effectively control and improve uric protein,anti dsDNA and kidney pathological changes in lupus murine.The therapeutic effects of NST and Allo SCT on lupus murine are comparable.But NST has weaker suppression to bone marrow function and faster recovery of hematopoietic function than Allo SCT.Incidences of complications and mortality related to transplantation are lower in NST group than in Allo SCT group,but acute GVHD are not more serious in NST group than in Allo SCT group.So NST is a safer and more effective treatment method than Allo SCT to lupus murine.