小鼠半相合脐血移植模型的建立及相关研究

发布时间：2018-06-13 21:27

本文选题：脐血移植 + 半相合　；参考：《上海交通大学》2008年硕士论文

【摘要】： 目的:建立小鼠半相合脐血移植模型,探讨多位点不相合脐血移植后造血及免疫重建特性。方法:经大剂量全身照射预处理BDF1小鼠后,经尾静脉输注新生第一天DBA/2小鼠的外周全血,移植后动态观察受体鼠的造血重建及急性移植物抗宿主病(GVHD)发生情况,并用流式双染色法进一步检测受鼠外周血、骨髓、脾和胸腺中粒系、淋巴系造血细胞的长期植入水平。结果:移植后小鼠的白细胞、血小板、血红蛋白分别在第18、21、18天明显回升,其中白细胞和血小板分别于第29天和36天恢复正常,而血红蛋白至第50天仍为部分恢复。受体鼠90%长期存活,且不发生明显的GVHD。移植后第50天流式细胞仪检测外周血中供鼠来源的造血细胞占总有核细胞的88.81%,其中含供者来源的粒细胞33.92%,T细胞16.83%;骨髓有核细胞以粒细胞和B细胞为主,分别占42.94%和37.24%;脾组织中仍残留较多宿主T细胞,占总T细胞的42.2%;胸腺组织中T细胞达到完全嵌合;外周血、骨髓和脾组织CD11c+树突状细胞均达到或接近完全嵌合。结论:单份新生小鼠外周血含有足够的造血干细胞,可作为脐血移植的替代品,能重建半相合小鼠的造血及免疫系统而不引起明显的GVHD,并可形成稳定的以供者细胞为主的嵌合体。免疫器官和外周血的免疫细胞得到有效重建。
[Abstract]:Objective: to establish mouse haploidentical umbilical cord blood transplantation model and to study the hematopoietic and immune reconstitution characteristics after multi-locus incompatible cord blood transplantation. Methods: BDF1 mice were pretreated with high dose whole body irradiation. Peripheral whole blood of DBA / 2 mice on the first day of newborn was infused via tail vein. The hematopoietic reconstitution and GVHD of acute graft versus host disease were observed dynamically after transplantation. The long-term implantation level of hematopoietic cells in peripheral blood, bone marrow, spleen, thymus and lymphoid line of recipient rats was further detected by flow double staining. Results: the white blood cells, platelets and hemoglobin of the transplanted mice increased significantly on the 18th day after transplantation. The white blood cells and platelets returned to normal on the 29th and 36th day respectively, while the hemoglobin recovered partially on the 50th day. 90% of the recipient mice survived for a long time, and no obvious GVHDs occurred. On the 50th day after transplantation, the peripheral blood donor hematopoietic cells from mice accounted for 88.81% of the total nucleated cells, in which the donor granulocytes 33.92% T cells were 16.83% and the bone marrow nucleated cells were mainly granulocytes and B cells. The percentage of T cells in spleen tissues was 42.94% and 37.24%, respectively. There were still many host T cells in spleen tissues, which accounted for 42.2% of total T cells; T cells in thymus reached complete chimerism; CD11c dendritic cells in peripheral blood, bone marrow and spleen were all or close to complete chimerism. Conclusion: the single newborn mouse peripheral blood contains enough hematopoietic stem cells and can be used as a substitute for umbilical cord blood transplantation. It can reconstruct the hemopoiesis and immune system of haploidentical mice without causing obvious GVHD, and can form stable chimeric donor cells. Immune cells of immune organs and peripheral blood were reconstructed effectively.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R-332;R457.7

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