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

作　　者：李红[1] 郭子宽[2] 李秀森[1] 江小霞[1] 朱恒[1] 要辉宇[1] 王晓燕[1] 苏永丰[1] 廖丽[3] 刘元林[1] 吴英[1] 张毅[1] 毛宁[1] 

机构地区：[1]军事医学科学院基础医学研究所细胞生物学研究室,北京市100850 [2]军事医学科学院放射与辐射医学研究所实验血液学研究室,北京市100850 [3]军事医学科学院307医院造血干细胞移植中心,北京市100071

出　　处：《组织工程与重建外科杂志》2010年第3期121-127,共7页Journal of Tissue Engineering and Reconstructive Surgery

基　　金：supported by the National Key Basic Research Program of China (Grant number 2005CB522705);National Natural Sciences foundation of China (Grant number30900568, 30600309, 30730043)~~

摘　　要：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.

关 键 词：急性移植物抗宿主病 抗原呈递细胞 免疫调节 体内间充质干细胞 T淋巴细胞 

分 类 号：R392.45[医药卫生—免疫学]