發(fā)布時(shí)間：2018-01-28 22:28

  本文關(guān)鍵詞： 人骨髓間充質(zhì)干細(xì)胞 外周血單個(gè)核細(xì)胞 動(dòng)員 NOD/SCID小鼠 異種移植物抗宿主病　出處：《第二軍醫(yī)大學(xué)》2006年博士論文　論文類(lèi)型：學(xué)位論文

【摘要】：目的 觀察第三方huBM-MSCs在體外對(duì)動(dòng)員后huPBMNCs免疫反應(yīng)的影響以及huBM-MSCs在人-NOD/SCID小鼠嵌合體中的作用。方法 1與huBM-MSCs共培養(yǎng),給予PHA刺激后檢測(cè)huPBMNCs的增殖,細(xì)胞周期及細(xì)胞表型以及培養(yǎng)上清中細(xì)胞因子含量。2動(dòng)員后huPBMNCs和/或huBM-MSCs經(jīng)尾靜脈輸注給亞致死照射預(yù)處理后的NOD/SCID小鼠,分析人源細(xì)胞植入,人淋巴細(xì)胞亞群分布及組織病理改變。結(jié)果 1 huBM-MSCs使活化的huPBMNCs增殖抑制,細(xì)胞周期阻滯在G_0/G_1期,HLA-DR表達(dá)減少,CD4~+CD25~+細(xì)胞比例上調(diào),sIL-2R、TNF-α以及IL-4分泌減少,IL-10分泌增加。2大部分嵌合體huCD45~+細(xì)胞植入率在20%以上,出現(xiàn)以體重減輕、血小板減少為主要臨床表現(xiàn),肝臟、肺臟的T細(xì)胞浸潤(rùn),組織細(xì)胞壞死,纖維化形成為主要靶器官病理?yè)p害的X-GVHD表現(xiàn),huBM-MSCs 1×10~6聯(lián)合輸注在同水平人源細(xì)胞植入條件下改善體重減輕現(xiàn)象,緩和CD4/CD8比例倒置,重度病理?yè)p傷較少,對(duì)其他指標(biāo)無(wú)顯著影響。結(jié)論 huBM-MSCs能夠在體外減弱動(dòng)員后huPBMNCs的免疫應(yīng)答。8×10~7動(dòng)員后huPBMNCs輸注給20cGy/min,3Gy照射后的NOD/SCID,可以較為簡(jiǎn)便地獲得X-GVHD模型。在這個(gè)模型中,單次輸注huBM-MSC本身無(wú)不良反應(yīng),并不加重X-GVHD,可能具有潛在的防治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.

【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類(lèi)號(hào)】：R392

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本文編號(hào)：1471721