间充质干细胞移植抑制小鼠急性移植物抗宿主病的实验研究(英文)

Experimental Research on Inhibition of Acute Graft-versus-Host Disease by Transplanted Mesenchymal Stem Cells in Murine Model

目的研究间充质干细胞的体内免疫调节活性。方法将C57/BL脾脏细胞输注入受亚致死量照射的BALB/c小鼠,建立急性移植物抗宿主病模型,受体小鼠或同时接受密质骨骨髓来源的间充质干细胞,流式细胞技术检测脾细胞表面表达的活性分子。结果模型经输注间充质干细胞后,鼠脾脏CD11b+细胞表达的CD86和CD69减少,提示抗原呈递细胞的成熟度下降。此外,作为一种效应T细胞早期活化和发育的标记,CD3+CD69+细胞/CD3+细胞的比值降低,导致脾内CD3+细胞的绝对和相对数目减少。但是,在同系脾细胞输注模型中,CD11b+细胞表面的CD69和MHCⅡ表达以及CD3+细胞表面的CD69不受影响。结论 MSCs可以分3个阶段抑制急性移植物抗宿主病,有望成为急性移植物抗宿主病的有效治疗手段,但仍需进行深入研究。

Objective To investigate the in vivo immunoregulatory activities of mesenchymal stem cells （MSCs）. Methods A murine aGvHD model was developed by transfusion of C57/BL splenocytes, with or without compact bone-derived MSCs, into sublethally irradiated BALB/c mice. The phenotypic features of the splenocytes were analyzed by flow cytometry after transplantation. Results MSCs infusion decreased the expression of CD86 and CD69 molecules on splenic CD11b＋ cells of aGvHD mice, suggesting of the decreased maturation of antigen presenting cells. Meanwhile, the ratio of CD3＋ CD69＋ to CD3＋ cells, a parameter for early activation and effector T cell formation, was dramatically down-regulated, resulting in the enhancement of the absolute and relative number of splenic CD3＋ cells by MSCs co-transfer. However, the expression level of MHC Ⅱ and CD69 on CD11b＋ cells and CD69 on CD3＋ cells were not affected in the syno-splenocyte infusion model. Conclusion The results here suggest that MSCs can inhibit aGvHD at the three development stages of specific cytotoxic T lymphocytes. Further investigations are needed for designing better strategies to manipulate aGvHD in clinical settings.