异基因骨髓源间充质干细胞移植形成稳定的嵌合体并诱导免疫耐受的研究

Allogeneic bone marrow derived mesenchymal stem cells transplantation leads to stable chimerism and induces donor specific tolerance

目的 探讨器官移植中间充质干细胞诱导免疫耐受的可能性。方法 雌性C57BL/6小鼠致死量照射后 ,移植同基因骨髓细胞和异基因骨髓源间充质干细胞 ,150d后以流式细胞仪检测其骨髓及脾脏的T细胞嵌合状态 ;以H3 TdR混合淋巴细胞反应 (MLR)和刀豆蛋白A(ConA)诱导增殖实验检测细胞移植组小鼠对供者来源细胞和有丝分裂原的反应性 ;以皮肤移植实验观测细胞移植组小鼠对供者来源组织器官移植物的反应性。结果 在细胞移植组小鼠脾脏中检测到供者来源T细胞占受者脾细胞 5 97% ;MLR反应中 ,细胞移植组小鼠的平均刺激指数 (SI)为 1 79,未处理组小鼠的平均SI为 7 2 8;在ConA诱导增殖实验中 ,细胞移植组小鼠的平均SI为 3 1 92 ,未处理组小鼠的平均SI为 3 4 99。细胞移植组小鼠供者来源皮肤移植物存活 >90d ,未处理组平均为 8d。结论 异基因骨髓源间充质干细胞移植后可形成稳定嵌合体 ,并诱导特异性免疫耐受的产生 。

Objective To investigate the possibility of immune tole rance induced by bone marrow-derived mesenchymal stem cells in allogeneic organ transplantation. Methods Allogeneic bone marrow-derived mesenchymal stem cells and syngeneic bone marrow cells were cotransplanted to lethally irradiated female C57BL/6 recipient mice. FACS was used to analyze the chimerism 150 days later. Mixed lymphocyte reaction and ConA induced proliferation test were performed to evaluate proliferative activity of mice spleen cells in cell-transplanted group. Skin transplantation test was done to observe immune response of cell-transplanted group mice against organ graft from donor mice. Results About 5 97% donor T cells were detected in splenocytes of cell-transplanted group mice. MLR showed that mean SI of cell-transplanted group mice was 1.79, and that of untreated group mice was 7 28. ConA induced proliferation test showed that mean SI of cell-transplanted group mice was 31 92; and that of untreated group mice was 34 99. Mean survival time of donor-derived skin graft in cell-transplanted group mice was more than 90 days; and that in untreated group mice was 8 days. Conclusion Our results showed for the first time that induction of stable mixed hematopoietic chimerism after allogeneic bone marrow derived mesenchymal stem cells transplantation lead to stable donor-specific tolerance in allogeneic host and skin graft survival from donor mice.