体外转染mFasL-cDNA小鼠骨髓细胞预防移植物抗宿主病的实验研究  

FasL-cDNA Transfected into Mouse Bone Marrow Cells Ex Vivo to Provent Graft Versus Host Disease

作　　者：徐之良[1] 邹萍[2] 刘凌波[2] 李爱香[2] 马艳萍[2] 

机构地区：[1]武汉大学人民医院儿科 [2]华中科技大学同济医学院附属协和医院血液病研究所,武汉430022

出　　处：《中国实验血液学杂志》2003年第5期512-515,共4页Journal of Experimental Hematology

基　　金：国家自然科学基因资助项目编号 39770 76 7

摘　　要：为了探讨通过Fas FasL途径清除骨髓移植物中T细胞后 ,预防移植物抗宿主病 (GVHD)的可能性 ,采用脂质体转移法将FasL cDNA转染雌性BALB/c小鼠骨髓细胞 ,证实其获得表达后 ,体外与雄性BAC (BALB/c×C57BL/ 6)小鼠骨髓移植物混合培养后输注给经致死照射的BALB/c鼠 ,然后观察受体鼠GVHD的表现、死亡率 ,进行组织病理学检查 ,骨髓细胞Y染色体及CFU S检测。结果表明 :实验组 10只小鼠 ,60天死亡 2只 ,4只有GVHD改变 ;对照组 10只 ,60天死亡 7只 ,10只均有GVHD改变 ;两组骨髓细胞Y染色体分析显示均有供体鼠来源的骨髓细胞植入 ;CFU S检测表明实验组动物体内 10天即有CFU S形成 ,移植后第 2 0天即达正常水平。结论 :转染mFasL cDNA小鼠骨髓细胞能有效地预防GVHD的发生 ,并能使受体造血功能获得重建。To explore the new approach to prevent graft ve rs us host disease (GVHD) by purging ex vivo T lymphocytes of bone marr ow graft through Fas-FasL way, FasL-cDNA was transfected into BALB/c mouse bon e marrow cells by liposome ex vivo. The transfected cells were cultu red together with BAC (BALB/c×C57BL/6) mouse bone marrow graft. The mixing bone marrow graft was infused into BALB/c mouse recipients after 60 Co-γ irradiation. The mortality, manifestation and pathologic change of GVHD in recip ient mice were observed. The CFU-S and Y chromosome from donor mice were detect ed. The results showed that compared with control group, the mortality in 60 day s of the recipients in the experimental group decreased (20% vs 70%, P<0.01) and the morbidity of GVHD lowered (40% vs 100%, P<0.01). The CFU-S counts for all groups were at normal level on 20 days after transplantation. The Y chromoso me from donor mice was discovered in 70% bone marrow nucleated cells of recipien t mice survived over 2 months in the experimental group. It is concluded that mF asL-cDNA transfected mouse bone marrow cells prevent GVHD after culturing toge ther with bone marrow graft, and accelerate hematopoietic reconstitution in reci pient mice.

关 键 词：FAS抗原 FAS配体 基因转染 骨髓移植 移植物抗宿主病 

分 类 号：R457.7[医药卫生—治疗学]