骨髓间充质干细胞抑制树突状细胞的分化和成熟.docVIP

  骨髓间充质干细胞抑制树突状细胞的分化 和成熟# 李银萍，欧阳静萍* 5 10 15 20 25 30 35 40 （武汉大学基础医学院病理生理学教研室，武汉 430071） 摘要：本研究的主要目的是探讨骨髓间充质干细胞（Bone marrow mesenchymal stem cells, ADSC）对单核细胞分化为树突状细胞（Dendritic cells, DC）的影响。方法：将分离培养 的 MSC 与单核细胞共培养，并加入树突状细胞分化因子 GM-CSF 和 IL-4。6 天后收集悬浮细 胞并用 TNFα诱导成熟 48 小时。分别用流式细胞术、混合淋巴细胞反应及扫描电子显微镜 检测细胞表型、刺激同种异体 T 淋巴细胞反应的功能及细胞形态。结果：同阳性对照 DC 相 比，与 MSC 共培养得到的细胞上 DC 相关分子的表达明显较低，包括 CD80，CD86，CD1a，CD83； 而 CD14 分子则持续性高表达；其刺激异基因 T 淋巴细胞增殖的能力亦显著降低。形态学上， 细胞胞体小，胞浆突起不明显甚至缺如。结论：MSC 抑制单核细胞向 DC 分化和成熟。 关键词：骨髓间充质干细胞；树突状细胞；单核细胞；分化 中图分类号：R36 Bone marrow Mesenchymal Stem Cells Inhibit Differentiation and maturation of Dendritic Cells LI Yinping, OUYANG Jingping (School of Basic Medical Science,Wuhan University, WuHan 430071) Abstract: In this study, we intend to study the effects of mesenchymal stem cells (MSC) on the differentiation of DC derived from monocytes. Methods: monocytes were cultured with human MSC in the presence of GM-CSF and IL-4. On day 6, cells in suspension were collected and TNF-α was added to induce maturation of DC for 48 hours. Phenotype, allogeneic stimulatory capacity and morphology of obtained cells were analyzed through cytometry, mixed lymphocyte reaction and microscopy. Results: Phenotypically, these cells expressed much lower levels of molecules, such as CD1a, CD86, CD80 and CD83, whereas they expressed persistently high level of CD14. Functionnally, their capacity to stimulate allogeneic T cells were significantly inhibited. Accordingly, these cells expressed rarely long and large cytoplasmic processes. Conclusion: MSC inhibit the differentiation of monocytes into DC. Keywords: Mesenchymal stem cells; Dendritic cells; Monocytes; Differentiation 0 引言 骨髓间充质干细胞（bone marrow mesenchymal stem cells, BMSC）是骨髓微环境中的重 要成员，具有高度异质性。早期的研究证实，BMSC 具有多向分化潜能，能分化为骨、软骨、 脂肪甚至心肌及神经组织细胞，并且能迁移到局部组织，修复组织的损伤。此外，它还参与 骨髓造血，通过分泌多种因子支持造血细胞的生长、增殖和分化[1]。近年来，大量研究发现 BMSC 在免疫调节中具有非常重要的作用，它能通过影响多种免疫细胞诱导免疫耐受[2,3]。 抗原递呈细胞（antigen-presenting cells, APC）是体内介导固有免疫和特异性免疫的重要 细胞。APC 通过对抗原的摄取、加工和递呈