关键词:骨髓移植,混合;移植物抗宿主病;移植物抗白血病
摘要 目的 :探讨在异基因骨髓移植治疗白血病中既控制移植物抗宿主病(GVHD)又同时保留移植物抗白血病(GVL)作用的移植方案。方法 :采用近交系小鼠移植模型,在异基因骨髓、脾细胞移植物中混合一定比例的同基因脾细胞,观察移植后受鼠GVHD死亡率、脾结节数、移植后不同时间骨髓造血重建细胞来源以及受鼠脾脏淋巴细胞对供、受鼠双方来源的刺激细胞增殖反应;采用L615小鼠白血病模型观察混合移植对荷瘤小鼠生存时间及死亡原因的影响。结果 :混合移植可以有效减轻GVHD,异基因造血免疫细胞在受鼠体内一过性存留并发挥移植物抗宿主反应,使荷瘤小鼠生存时间明显延长。结论 :异基因骨髓、脾细胞移植物中混合一定比例的同基因脾细胞使移植受鼠体内既具有主要组织相容性抗原复合物(MHC)不合的免疫活性细胞发挥一过性GVL作用,同时减轻了异基因骨髓移植的严重GVHD。
Study of experimental mixed bone marrow transplantation Luo Hui* , Yang Pingdi, He Fuchu.* Department of Hematology and Oncology,Naval General Hospital,Beijing 100037
Abstract Objective: To explore strategies for preventing graft versus host disease (GVHD) while preserving graft versus leukemia (GVL) effects in allogeneic bone marrow transplantation(BMT). Methods: Allogeneic bone marrow and spleen cells mixed with syngeneic spleen/bone marrow cells were transplanted into lethally irradiated inbred mice. The mortality of the recipient mice from GVHD, the number of CFU-S, the origin of the bone marrow cells responsible for the reconstitution at different time after transplantation and the proliferative reaction against the stimulating cells from the syngeneic or allogeneic mice were observed and compared with those in the conventional syngeneic and allogeneic BMT. L615 leukemia model was used to evaluate the GVL effect of mixed BMT. Results: Lethal GVHD was effectively prevented by the syngeneic spleen cells which showed no harmful effect on the CFU-S reconstitution. The medium survival time of the mixed transplanted L615 mice was significantly prolonged.Conclusion: The grafts composed of allogeneic bone marrow and spleen cells mixed with syngeneic spleen cells, make the recipient mice have transient GVL effects resulted from the MHC mismatched immunocompetent cells and alleviated the severe GVHD of allogeneic BMT.
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