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間充質(zhì)干細胞抑制T淋巴細胞增殖減輕移植物抗宿主病機制研究

發(fā)布時間:2018-02-13 15:34

  本文關(guān)鍵詞: 間充質(zhì)干細胞 T淋巴細胞 TGF-β_1 HGF GVHD 出處:《鄭州大學》2006年碩士論文 論文類型:學位論文


【摘要】:背景與目的: 間充質(zhì)干細胞(Mesenchymal stem cells,MSCs)是骨髓非造血細胞中成體干細胞中的一種,具有很強的自我更新能力和多向分化潛能。在體外不同分化條件的誘導下,可以形成成骨細胞、軟骨細胞或脂肪細胞等,并且克隆后的細胞具有類似分化潛能,充分證明了間充質(zhì)干細胞是多能分化細胞。除在骨髓中發(fā)現(xiàn)間充質(zhì)干細胞外,在骨骼肌、心肌、真皮,以及腦和外周血中,也發(fā)現(xiàn)有類似骨髓間充質(zhì)干細胞(BM-MSCs)生物學特性和表面標記的間充質(zhì)干細胞。間充質(zhì)干細胞表型不均一,,分別具有間充質(zhì)細胞、上皮細胞和內(nèi)皮細胞的特點。對人體外擴增的BM—MSCs的研究結(jié)果顯示一致表達SH2、SH3、CD29、CD44、CD77、CD90、CD106、CD120a、CD124等抗原,不表達造血干細胞(HSC)的標志性抗原CD14、CD34、CD45。但是目前還沒有特異的表面標記來證實間充質(zhì)干細胞。動物實驗和臨床研究均發(fā)現(xiàn),異基因造血干細胞移植時共同輸入供體間充質(zhì)干細胞可以降低移植失敗率并減輕移植物抗宿主病(GVHD)。具體機制尚不明確,大多數(shù)學者認為間充質(zhì)干細胞可能通過抑制T淋巴細胞增殖來減輕移植后GVHD,而這種抑制作用是通過分泌可溶性細胞因子實現(xiàn)的,最受關(guān)注的細胞因子是轉(zhuǎn)化生長因子-β_1(TGF-β_1)和肝細胞生長因子(HGF)。 本實驗通過體外培養(yǎng)間充質(zhì)干細胞(Mesenchymal stem cells,MSCs)探索其鑒定方法,觀察間充質(zhì)干細胞的生物學特性及TGF-β_1和HGF的表達,通過與T淋巴細胞的混合培養(yǎng)研究其抑制T淋巴細胞增殖,減輕GVHD的機制。 材料與方法:
[Abstract]:Background and purpose:. Mesenchymal stem cells (MSCs) is one of the adult stem cells in bone marrow non-hematopoietic cells. Chondrocytes, adipocytes, etc., and the cloned cells have similar differentiation potential, which fully proves that mesenchymal stem cells are pluripotent cells, except mesenchymal stem cells found in bone marrow, skeletal muscle, myocardium, dermis, And in the brain and peripheral blood, we also found BM-MSCslike mesenchymal stem cells with different phenotypes, and mesenchymal stem cells with mesenchymal cells. The characteristics of epithelial cells and endothelial cells. The results of BM-MSCs amplification in human body showed that the antigens SH2OSH3ONCD29, CD44, CD770, CD90, CD106, CD120a, CD124, and so on, were expressed in a consistent manner. But there is no specific surface marker to confirm mesenchymal stem cells. Animal experiments and clinical studies have found that, Allogeneic hematopoietic stem cell transplantation combined with donor mesenchymal stem cells can reduce graft failure rate and alleviate graft versus host disease (GV HDD). The mechanism is not clear. Most researchers believe that mesenchymal stem cells may reduce GVHD after transplantation by inhibiting T lymphocyte proliferation, which is achieved by secreting soluble cytokines. The most concerned cytokines were transforming growth factor- 尾 (TGF- 尾) and hepatocyte growth factor (HGF- 尾). In this experiment, mesenchymal stem cells were cultured in vitro to explore the identification of mesenchymal stem cells. The biological characteristics of mesenchymal stem cells and the expression of TGF- 尾 1 and HGF were observed. The proliferation of T lymphocytes was inhibited by co-culture with T lymphocytes. The mechanism of alleviating GVHD. Materials and methods:
【學位授予單位】:鄭州大學
【學位級別】:碩士
【學位授予年份】:2006
【分類號】:R392

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