小鼠混合骨髓移植中脾细胞诱导持久稳定嵌合体的作用

Efficacy of splenocytes in inducing stable long-term chimerism in murine mixed haploidentical MHC matched bone marrow transplant model

目的通过小鼠混合骨髓移植模型,将同基因和半相合异基因小鼠骨髓细胞和不同比例脾细胞混合移植给受鼠,探讨诱导持久稳定嵌合体、减轻严重移植物抗宿主病(GVHD)的方法。方法受鼠60Co全身照射,混合输入同基因和半相合异基因供鼠骨髓,同时将两者脾细胞按不同比例混合回输。测定嵌合体形成,观察GVHD表现及病理学改变,监测移植鼠生存率。结果小鼠移植后全部存活超过90 d,半相合异基因小鼠脾细胞输注剂量和比例对嵌合体形成的水平和嵌合状态的稳定性有显著影响。结论调整半相合异基因与同基因小鼠脾细胞输注剂量和比例对诱导异体持久植活、避免严重的GVHD的出现具有实际意义。

Objective To explore the method of inducing stable chimerism without severe graft versus host disease （GVHD） in murine mixed transplant model. Methods Recipient mice given ^60Co whole-body irradiation were infused with syngeneic and H-2 haploidentical matched bone marrow plus different proportion of splenocytes. The level of the chimerism of the recipient mice was detected by flow cytometry. The manifestations and histopathological examination of GVHD were observed. The mortality of the recipient mice from GVHD was observed. Results All the mice survived over 90 days. The dose of H-2 haploidentical matched splenocytes showed a great influence on the level and stability of chimerism. Conclusion It is critical to adjust the dose of H-2 haploidentical matched and syngeneic splenocytes in inducing stable chimerism and avoiding GVHD.