受体大鼠非清髓嵌合的建立及对供体细胞反应性的监测

An experimental study of immune depression to donor origin cells induced by the mixed chimera after sublethal whole body irradiation

目的:通过非清髓方式诱导嵌合体而产生免疫抑制。方法:动物分为三组:A组(BMC移植组)经全身辐照雌性SD大鼠于D0经尾静脉输注雄性Wistar大鼠骨髓细胞(BMC)。B组(BM-MSCs移植组)经全身辐照雌性SD大鼠于D0经尾静脉输注雄性Wistar大鼠骨髓间充质干细胞(BM-MSCs)。C组(对照组)经全身辐照大鼠于D0经尾静脉输注生理盐水0.8mL。随后测定异基因嵌合体量的变化,及单向混合淋巴细胞培养的刺激效应。结果:A、B组动物在21天后均检测到一定比例的嵌合体细胞,流式细胞仪检测A组嵌合率明显高于B组(P<0.05)。两组在预处理后第35天观测发现嵌合率均明显降低。A组较B组和C组的受体淋巴细胞增殖显著减弱,B组较C组也显著减弱。结论:选用的非清髓预处理方案可使受者体内形成混合性嵌合体,大鼠耐受性较好,移植后供者细胞植入一定时间内嵌合稳定、死亡率低,是一种有效的移植免疫抑制诱导方法。

Objective：To investigate the immune depression to donor-origin cells induced by the Mixed Chimera after sublethal whole body irradiation. Methods： Recipients in the experiment were Wistar and SD rat, and Wistar rats were selected as the donor. Donor and recipient rats were divided randomly into three groups. Recipient were conditioned with sublethal whole body irradiation （WBI）. Group A was infused with bone marrow cells （BMC） of Wistar rats;group B infused with bone marrow mesenehymal stem cells （BM-MSCs）of Wistar rats;and group C with normal saline. Then they were administered cytoxan（CTX） by intraperitoneal injection. The mechanisms for immune depression were explored by performing mixed lymphocyte reaction （MLR）. Results： The results showed that donor lymphoid chimeras cotdd be found in the immune depression SD rats and chimerac cells in group A was more than in group B by FCM assay （ P 〈 0.05）. The SD rats of both group A and group B were specifically tolerant to the stim^ator cells from Wistar rats in MLR assay. Condusion： These results suggest that conditioned non- myeloablative regimens for allogeneic BMC/BM-MSC transplantation can successfully establish mixed chimeras model from Wistar to SD rots and induce a specific immune depression in SD rats.