MHC不相合的双份鼠胎血移植后受体鼠混合嵌合体形成(英文)

Double Chimerism in Recipient by Transplantation of Two Allogeneic MHC-Mismatched Mouse Fetal Blood Units

本室已经建立了MHC不相合单份鼠胎血同种移植的小鼠模型。基于脐血造血干细胞的免疫学特性及临床实践 ,我们认为脐血移植成功的关键除了选择尽可能相合的供者外 ,保证移植细胞的数量更为重要。因此 ,为了提高移植干细胞的数量 ,本研究在前期工作的基础上 ,探讨MHC不相合的双份鼠胎血混合移植的可能性。研究结果表明 ,混合移植组 4 0只受鼠中有 2 6只在 6 0天的观察期内存活下来 ;应用PCR及流式细胞术均检测到受鼠体内有混合嵌合体的形成 ;此外 ,皮肤移植试验也发现受鼠已被诱导形成对供鼠的特异性免疫耐受 ;小肠组织的病理切片显示受鼠仅表现出轻度GVHD。结论 :MHC不相合的双份鼠胎血能够同时植入 ,重建受鼠的免疫与造血系统 ,这为拓宽脐血的临床应用 ,使更多患者能够有机会接受脐血移植做了有益的尝试。

We have constituted a mouse model for fetal blood transplantation(FBT) to cross over major histocompatibility complex(MHC) without causing serious GVHD. It seems that full matching at the MHC appears not necessory for FBT, while the nucleated cell dose is critical. Two fetal blood units were combined from different donors to increase the stem/progenitor cell dose so as to explore the possibility of MHC mismatched allogeneic transplantation. 26 out of 40 mice in mixed FBT group survived in the observation period of 60 days after transplantation without obvious GVHD. Double chimerism was demonstrated by PCR and flow cytometric analysis; and skin transplantation test proved the induction of donor specific immune tolerance. Our data suggest that two MHC mismatched allogeneic donor fetal blood units could simultaneously engraft and reconstitute immune and hematopoietic system in a mouse model. The result may be beneficial for the expansion of cord blood application and enables more patients to share the advantages of cord blood transplantation.