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[非清髓性预处理单倍型相合造血干细胞移植恒河猴模型的建立]

[Establishment of rhesus model for haploidentical hematopoietic stem cell transplantation with nonmyeloablative conditioning].

作者信息

Liu Li-Hui, Sun Qi-Yun, Hu Kai-Xun, Fan Chuan-Bo, Huang Ya-Jing, Bian Li, Xiao Xiu-Bin, Yao Bo, Guo Mei, Yu Chang-Lin, Ai Hui-Sheng

机构信息

Department of Hematology, The Affiliated Hospital of Academy of Military Medical Sciences, Beijing 10039, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005 Aug;13(4):677-82.

PMID:16129059
Abstract

To study if rhesus haploidentical hematopoietic stem cell transplantation model can be established by non-myeloablative conditioning, parent monkeys were used as donors, offspring monkeys were used as recipients. The recipient monkeys received a nonmyeloablative conditioning consisting of fludarabine, cyclophosphamide, total body irradiation and rabbit anti-human thymocyte globulin. Cyclosporine, mycophenolate mofetil and anti CD25 antibody were used for GVHD prevention. Donor mobilized peripheral blood stem cells were transplantated on day 0. Hematopoietic recovery, chimerism level, GVHD were assessed regularly. The results indicated that hematopoietic recoveries in all 4 cases were observed within 8 days after transplantation. Donor hematopoietic chimerism could be induced in all cases, chimerism analysis showed full donor chimerism (FDC) in case 3 and 4, and II to III grade GVHD developed on day 12 and 14. In case 1, only low level donor chimerism was detected on day 7, and transplantation rejection happened eventually. Unfortunately, kidney failure happened in case 2 after conditioning and died several days later, chimerism analysis showed 50% donor rate on day 7. It is concluded that the rhesus transplantation model was successfully established by nonmyeloablative conditioning for striding over the MHC barrier. This rhesus monkey model would provide a basis for future research.

摘要

为研究非清髓性预处理是否能建立恒河猴半相合造血干细胞移植模型,以亲代猴为供体,子代猴为受体。受体猴接受由氟达拉滨、环磷酰胺、全身照射和兔抗人胸腺细胞球蛋白组成的非清髓性预处理。使用环孢素、霉酚酸酯和抗CD25抗体预防移植物抗宿主病(GVHD)。在第0天移植供体动员的外周血干细胞。定期评估造血恢复、嵌合水平和GVHD。结果表明,4例均在移植后8天内观察到造血恢复。所有病例均可诱导供体造血嵌合,嵌合分析显示第3例和第4例为完全供体嵌合(FDC),并在第12天和第14天发生Ⅱ至Ⅲ级GVHD。第1例在第7天仅检测到低水平供体嵌合,最终发生移植排斥。不幸的是,第2例在预处理后发生肾衰竭,数天后死亡,嵌合分析显示第7天供体率为50%。结论是通过非清髓性预处理成功建立了跨越主要组织相容性复合体(MHC)屏障的恒河猴移植模型。该恒河猴模型将为未来的研究提供基础。

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