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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。
In order to investigate whether non-myeloablative preconditioning can establish a monocytogenetic hematopoietic stem cell transplantation model, healthy, haploidentical macaques were used as donors and offspring as recipients. Receptor with fludarabine + cyclophosphamide + whole body irradiation + rabbit anti-human thymocyte globulin for non-myeloablative pretreatment; with cyclosporine A, mycophenolate mofetil, mouse anti-human CD25 monoclonal antibody as Graft-versus-host disease (GVHD) prophylaxis; donor-mobilized peripheral blood stem cells on day 0; regular monitoring of hematopoietic recovery, hematopoietic chimerism, and GVHD. The results showed that 4 cases of non-myelocytic non-myeloablative preconditioning, hematopoietic recovery within 8 days after transplantation can restore early donor hematopoietic stem cell transplantation; Example 3, Example 4 implantation was successful, 12,14 days after transplantation Grade II-III GVHD occurred. In case 1, a low proportion of donor grafts were implanted 7 days after transplantation, and finally graft rejection occurred. In case 2, donor composition was 50% 7 days after grafting and early death due to renal failure. Conclusion: The non-myeloablative preconditioning can cross the MHC barrier of haploidentical macaques and successfully establish haploidentical hematopoietic stem cell transplantation model, which lays the foundation for further experimental research.