低氧对脂肪源间充质干细胞生理特性的影响

发布时间：2018-06-16 15:38

本文选题：脂肪源间充质干细胞 + 低氧　；参考：《中国协和医科大学》2007年硕士论文

【摘要】： 间充质干细胞具有强大的自我更新和多系分化潜能，体内外实验表明其可以向神经细胞、血管内皮细胞、上皮细胞、脂肪细胞、成骨细胞及成软骨细胞分化，因而在组织修复上有着诱人的前景。另一方面，间充质干细胞有独特的免疫抑制功能，能够抑制T细胞的增殖、树突状细胞的成熟，在抑制排斥反应和治疗自身免疫性疾病方面是一可行的临床选择。因此如何优化干细胞的体外培养条件，以更好的模拟干细胞的体内状态，以及在体外培养扩增出更适合移植的种子细胞，又是一个十分重要的课题。目前对于干细胞生理特性的体外研究主要是在20％O_2的培养条件下进行，并不符合体内的微环境。本文初步探讨了在2％O_2的培养条件下，脂肪源间充质干细胞不同方面的生理特性是否有所改变，一共包括三部分的内容。第一部分研究了低氧对脂肪源间充质干细胞基本表型、干细胞的标志性基因以及迁移能力影响。结果提示2％O_2的培养条件下，，其基本表型没有改变，干细胞的标志性基因OCT-4和nanog可以保持表达；2％O_2的低氧条件使脂肪源间充质干细胞表面CXCR4表达明显增加，迁移试验证实这些细胞向SDF因子的迁移能力提高。第二部分研究了脂肪来源的间充质干细胞对T细胞的免疫抑制功能以及低氧对间充质干细胞免疫特性的影响，体外实验观察了2％O_2的培养条件下，脂肪来源的间充质干细胞表面免疫相关分子的表达。结果提示脂肪源间充质干细胞与T细胞的比率为1∶1时可显著抑制T细胞的增殖，而AMSCs和T细胞的比率为1∶10和1∶100时没有明显抑制效果；低氧培养的脂肪源间充质干细胞HLA-DR分子及其反式激活因子表达上调。第三部分研究了脂肪源间充质干细胞的成骨和成脂分化潜能，以及移植到经全身照射过的小鼠体内后，用PET检测AMSCs的分布情况。结果提示脂肪来源的间充质干细胞可向成骨细胞、脂肪细胞分化。AMSCs移植后在肺部潴留较多，另外主要分布于胃肠道，肝脏等组织。
[Abstract]:Mesenchymal stem cells have the potential of self-renewal and multi-lineage differentiation. In vitro and in vivo, mesenchymal stem cells can differentiate into neural cells, vascular endothelial cells, epithelial cells, adipocytes, osteoblasts and chondroblasts. As a result, there are attractive prospects for tissue repair. On the other hand, mesenchymal stem cells have a unique immunosuppressive function, which can inhibit the proliferation of T cells and the maturation of dendritic cells. It is a feasible clinical choice in inhibiting rejection and treating autoimmune diseases. Therefore, how to optimize the culture conditions of stem cells in vitro, to better simulate the status of stem cells in vivo, and in vitro culture to expand more suitable for transplantation of seed cells, is also a very important issue. At present, the physiological characteristics of stem cells are mainly studied under the culture condition of 20g / O _ 2, which does not conform to the microenvironment in vivo. In this paper, we discussed whether the physiological characteristics of adipose derived mesenchymal stem cells have changed in different aspects under the condition of 2ostack 2, which consists of three parts. In the first part, we studied the effects of hypoxia on the basic phenotype of adipose derived mesenchymal stem cells, the signature genes and migration ability of stem cells. The results showed that the basic phenotype of the stem cells remained unchanged under the culture condition of 2O 2, and the expression of CXCR4 on the surface of adipose derived mesenchymal stem cells was significantly increased by the hypoxia condition of OCT-4 and nanog, and the expression of CXCR4 on the surface of adipose derived mesenchymal stem cells was significantly increased. Migration assay confirmed that the migration ability of these cells to SDF factors was increased. In the second part, the immunosuppressive effect of adipose derived mesenchymal stem cells on T cells and the effects of hypoxia on the immune properties of mesenchymal stem cells were studied. Expression of immune-associated molecules on the surface of adipose derived mesenchymal stem cells. The results suggested that the ratio of adipose derived mesenchymal stem cells to T cells was 1:1, but the ratio of AMSCs to T cells was 1:10 and 1: 100. The expression of HLA-DR and its transactivator was up-regulated in adipose derived mesenchymal stem cells cultured in hypoxia. In the third part, the osteogenic and adipogenic potential of adipose derived mesenchymal stem cells (MSCs) was studied, and the distribution of AMSCs was detected by PET after transplantation to mice irradiated with whole body. The results suggested that adipose-derived mesenchymal stem cells could be transferred to osteoblasts. After transplantation of adipocyte differentiation. AMSCs were mainly distributed in gastrointestinal and liver tissues.
【学位授予单位】：中国协和医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R329

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