人间充质干细胞对动员后外周血单个核细胞免疫反应的影响及在人—鼠嵌合体中的作用

发布时间：2018-01-28 22:28

本文关键词： 人骨髓间充质干细胞外周血单个核细胞动员 NOD/SCID小鼠异种移植物抗宿主病　出处：《第二军医大学》2006年博士论文　论文类型：学位论文

【摘要】：目的观察第三方huBM-MSCs在体外对动员后huPBMNCs免疫反应的影响以及huBM-MSCs在人-NOD/SCID小鼠嵌合体中的作用。方法 1与huBM-MSCs共培养,给予PHA刺激后检测huPBMNCs的增殖,细胞周期及细胞表型以及培养上清中细胞因子含量。2动员后huPBMNCs和/或huBM-MSCs经尾静脉输注给亚致死照射预处理后的NOD/SCID小鼠,分析人源细胞植入,人淋巴细胞亚群分布及组织病理改变。结果 1 huBM-MSCs使活化的huPBMNCs增殖抑制,细胞周期阻滞在G_0/G_1期,HLA-DR表达减少,CD4~+CD25~+细胞比例上调,sIL-2R、TNF-α以及IL-4分泌减少,IL-10分泌增加。2大部分嵌合体huCD45~+细胞植入率在20%以上,出现以体重减轻、血小板减少为主要临床表现,肝脏、肺脏的T细胞浸润,组织细胞坏死,纤维化形成为主要靶器官病理损害的X-GVHD表现,huBM-MSCs 1×10~6联合输注在同水平人源细胞植入条件下改善体重减轻现象,缓和CD4/CD8比例倒置,重度病理损伤较少,对其他指标无显著影响。结论 huBM-MSCs能够在体外减弱动员后huPBMNCs的免疫应答。8×10~7动员后huPBMNCs输注给20cGy/min,3Gy照射后的NOD/SCID,可以较为简便地获得X-GVHD模型。在这个模型中,单次输注huBM-MSC本身无不良反应,并不加重X-GVHD,可能具有潜在的防治aGVHD作用。
[Abstract]:Objective To observe the effect of third huBM-MSCs in the immune response to huPBMNCs after mobilization in vitro and huBM-MSCs in human -NOD/SCID mouse chimeras in vitro. Methods 1 co cultured with huBM-MSCs, detection of huPBMNCs proliferation stimulated by PHA, cell cycle and cell phenotype and cytokine content in the culture supernatant of.2 mobilized huPBMNCs and / or huBM-MSCs intravenous infusion of sublethal irradiation of NOD/SCID mice, analysis of human cell engraftment, subsets and pathological changes of human lymphocytes. The results of 1 huBM-MSCs activated huPBMNCs proliferation inhibition, cell cycle arrest in G_0/G_1 phase, the expression of HLA-DR decreased, the proportion of CD4~+CD25~+ cells increased, sIL-2R, TNF- alpha and IL-4 reduce the secretion, increased secretion of IL-10.2 most chimera huCD45~+ cell implantation rate in more than 20%, by weight loss, thrombocytopenia was the main clinical table Now, liver, lung T cell infiltration, tissue necrosis, X-GVHD fibrosis formed as the main target organ pathological damage, huBM-MSCs 1 * 10~6 infusion in the same level of human cells implanted under the condition of improved weight loss, moderate CD4/CD8 ratio inversion, less severe pathological damage, no significant effect on other indexes. Conclusion huBM-MSCs in vitro can weaken the immune response of.8 mobilized huPBMNCs x 10~7 mobilization after infusion of huPBMNCs to 20cGy/min, 3Gy after the irradiation of NOD/SCID, can easily get X-GVHD model. In this model, a single infusion of huBM-MSC itself without adverse reaction, does not aggravate X-GVHD, may have a potential role in the prevention and treatment of aGVHD.

【学位授予单位】：第二军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392

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