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H-2半相合小鼠非清髓性骨髓移植模型的建立

Establishment of a murine model of H-2 haploidentical nonmyeloablative bone marrow transplantation
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摘要 目的 建立H 2半相合小鼠非清髓性骨髓移植模型。方法 用氟达拉滨、阿糖胞苷、环磷酰胺联合60 Co 2Gy全身照射组成预处理方案 ,以C5 7BL/ 6J(H 2 b)为供鼠 ,以C5 7BL/ 6J×BALB/c杂交F1代小鼠为受鼠 ,进行H 2半相合骨髓移植 ,采用环孢素A联合甲氨蝶呤预防急性移植物抗宿主病 (aGVHD)。观察移植后小鼠造血恢复、aGVHD发生率及死亡率 ,5 0d内存活率。结果 移植小鼠平均在 (1 2 .0± 1 .6 )d造血恢复 ,仅接受预处理而不输注供鼠细胞的小鼠在 (1 3.5± 2 .0 )d恢复自身造血 ;移植小鼠移植后 +7d到 +45d内均可检测到供、受者混合造血细胞嵌合体 ;移植后 +2 2d~+2 5d小鼠出现典型的aGVHD症状。环孢素A联合甲氨蝶呤预防方案可有效降低aGVHD的发生率 ,并减轻其严重程度 ;aGVHD死亡率为 6 0 %,5 0d内存活率为 70 %。结论 以氟达拉滨、阿糖胞苷、环磷酰胺联合全身照射组成的非清髓性预处理方案 ,可在H 2半相合小鼠间进行成功的骨髓移植 ,并可产生稳定的供、受者混合造血细胞嵌合体。 Objective To establish a murine model of H-2 haploidentical nonmyeloablative bone marrow transplantation.Methods Under the preconditioning regimen, fludarabine, Ara-C, CTX in combination with 2 Gy whole body irradiation, the murine model was established by using C57BL/6J(H-2 b)mouse as donor, and (C57BL/6J×BALB/c) F1 mouse as the recipient. The transplanted murine was given CsA and MTX for acute graft versus host disease (aGVHD) prophylaxis. Hematopoietic recovery, aGVHD and the survival rate of the murine in the 50 days were observed.Results Hematopoietic recovery of the transplanted mice was observed in ( 12.0± 1.6) days, and hematopoietic recovery of non-transplanted mice was observed in ( 13.5± 2.0) days. The mixed hematopoietic cell chimerism could be detected in the spleen from 7th day to 45th day posttransplantion. The transplanted mice developed typical aGVHD from 22nd day to 25th day posttransplantion. CsA with MTX could effectively reduce the incidence of aGVHD and alleviate its severity. The mortality of aGVHD was 60 % and the survival rate was 70 % in 50 days. Conclusion Under the preconditioning regimen consisting in fludarabine, Ara-C, CTX in combination with 2 Gy total body irradiation, bone marrow transplantation can be successfully performed and the stable mixed hematopoietic chimerism can be established in H-2 haploidentical mice.
出处 《中华器官移植杂志》 CAS CSCD 北大核心 2004年第6期368-370,共3页 Chinese Journal of Organ Transplantation
基金 国家 8 6 3主体专项课题资助项目 ( 2 0 0 2AA2 16 0 81)
关键词 小鼠 GVHD 骨髓移植 联合 移植后 非清髓性 C57BL/6 受者 结论 目的 Transplantation conditioning Bone marrow transplantation Graft vs host disease
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参考文献5

  • 1Storb R, Schamplin R, Riddell S, et al. Non-myeloabalative transplants for malignant disease: Washinton: Hematology 2001 The American Society of Hematology Education Program Book, 2001,375-391. 被引量:1
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  • 3Jennifer E, Woodward, Abdus Salam. FIt3-L augments the engraftment of donor-derived bone marrow cells when combined with sublethal irradiation and costimulatory (CD28/B7and CD40/CD40L)blockade. Cell Transplantation, 2002,11:147-159. 被引量:1
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