Mechanisms of differentiation of mesenchymal stem cells and their functional roles in diseases

间充质干细胞的分化机制及其在疾病中的功能作用

基本信息

批准号：
15580262
负责人：
KOTANI Takao
金额：
$ 2.3万
依托单位：
Osaka Prefecture University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

To clarify the differential mechanisms of mesenchymal cells, the following experiments were performed using undifferentiated mesenchymal stem cell lines (MT-9, TSD-B9). MT-9 is a cell line isolated from a rat malignant fibrous histiocytoma having pluripotential differentiation, and TSD-B9 is a cell line derived from a rat malignant teratoma, of which the origin is gonadal germ cells capable of differentiating towards endodermal, mesodermal and ectodermal tissues.1.Osteoblastic differentiation : The addition of a supplement for osteoblastic differentiation, including BMP-2, to these cell lines increased calcified areas, demonstrable by von Kossa stain, and showed an elevated alkaline phosphatase in supernatants ; these are indicators of osteoblastic differentiation.2.Lipoblastic differentiation : The addition of a supplement for lipoblastic differentiation, including indomethacin, dexamethasone and insulin, to these cell lines increased the number of cells having oil red O-stainable lipids in the cytoplasm. The stain is useful for detection of lipoblastic cells.3.Myofibroblastic differentiation : The treatment with TGF-β1, a fibrogenic factor in fibrotic diseases, increased the number of cells immuno-reacting to α-smooth muscle actin (α-SMA) ; the increase was demonstrated by the western blotting. α-SMA-expressing cells are regarded as myofibroblasts.5.These studies partly clarified the mechanisms of mesenchymal differentiation, and these cell lines would prove useful for investigating the mechanisms.6.Furthermore, a new cell line was established from a rat malignant fibrous histiocytoma arising in the subcutis, showing histiocytic nature, and another cell line was isolated from a rat malignant schwannoma generating from the uterine cervix. These cell lines would become also beneficial tools for studies on mesenchymal differentiation.

为了阐明间充质细胞的差异机制，使用未分化的间充质干细胞系（MT-9，TSD-B9）进行以下实验。 MT-9是从具有多能分化的大鼠恶性纤维组织核糖核细胞瘤分离的细胞系，TSD-B9是一种细胞系，源自大鼠恶性肿瘤的细胞系，其起源是性腺生殖细胞，能够在其上朝着内二基，中胚层和皮肤皮肤病剂的分化。包括BMP-2在内的分化与这些细胞系增加了钙化区域，可通过von Kossa染色证明，并在上清液中显示出升高的酒精磷酸酶。这些是成骨细胞分化的指标。2。脂肪细胞分化：添加用于脂肪细胞分化的补充剂，包括吲哚美辛，地塞米松和胰岛素，增加了这些细胞系增加了在细胞质中具有油还原性脂质的细胞的数量。该污渍可用于检测脂肪细胞细胞。3。肌纤维细胞分化：用TGF-β1治疗纤维化疾病中的纤维化因子，增加了对α-光滑肌肉肌动蛋白（α-SMA）免疫反应的细胞数量；α-SMA）；蛋白质印迹证明了这一增加。表达α-SMA表达细胞被认为是肌纤维细胞。5。这些研究部分澄清了间质分化的机制，这些细胞系将被证明对研究机制很有用。6.furthermore。furthermore，一种新的细胞系，是从大鼠恶性纤维组织中产生的一个孤立性的较大纤维细胞的新细胞，该细胞属性是由一个隔离的细胞群，该细胞属性是孤立的。从子宫宫颈产生的雪旺瘤。这些细胞系也将成为研究间充质分化的有益工具。