猕猴非清髓单倍相合造血干细胞移植模型的建立  

Establishment of Rhesus Model for Haploidentical Hematopoietic Stem Cell Transplantation with Nonmyeloablative Conditioning

作　　者：刘丽辉[1] 孙琪云[1] 胡锴勋[1] 范传波[1] 黄雅静[1] 边莉[1] 肖秀斌[1] 姚波[1] 郭梅[1] 余长林[1] 艾辉胜[1] 

机构地区：[1]军事医学科学院附属医院血液科,北京100039

出　　处：《中国实验血液学杂志》2005年第4期677-682,共6页Journal of Experimental Hematology

基　　金：国家"863"资助;编号2002AA216081

摘　　要：为了研究用非清髓预处理是否能建立猕猴单倍相合造血干细胞移植模型,采用健康、单倍相合的亲代猕猴为供者,子代为受者。受体用氟达拉滨+环磷酰胺+全身照射+兔抗人胸腺细胞球蛋白作非清髓性预处理;用环胞菌素A、霉酚酸酯、鼠抗人CD25单克隆抗体作为移植物抗宿主病(GVHD)预防方案;第0天输注供者动员后的外周血造血干细胞;定期监测造血恢复、造血嵌合水平和GVHD发生等情况。结果表明:4例猕猴用非清髓性预处理后,移植后8天内造血均能恢复,早期均有供者造血干细胞植入;例3、例4植入成功,在移植后12、14天出现Ⅱ-Ⅲ度GVHD;例1在移植后7天低比例供者植入,最后出现移植排斥;例2在移植后7天供者成分占50%,后因肾衰早期死亡。结论:用非清髓性预处理可以跨越单倍相合猕猴的MHC屏障,成功建立了单倍相合造血干细胞移植的模型,为进一步实验研究奠定了基础。To study if rhesus haploidentical hematopoietic stem cell transplantation model can be established by nonmyeloablative 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, chimerismlevel, 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 l, 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.

关 键 词：猕猴 造血干细胞移植 单倍型相合造血干细胞移植 非清髓预处理 

分 类 号：R457.7[医药卫生—治疗学]