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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15580262/
• 关键词: Mesenchymal differentiation; Undifferentiated stem cell; Malignant fibrous histiocytoma; Malignant teratoma; Osteoblastic differentiation; Lipoblastic differentiation; Myofibroblastic differentiation; Rat tumor model; 間葉系分化; 多分化能幹細胞; 子宮内膜肉腫; TG

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分化机制，使用未分化间充质干细胞系（MT-9、TSD-B 9）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细胞瘤分离的细胞系，TSD-B 9是从大鼠恶性畸胎瘤衍生的细胞系，其来源是能够向内胚层、中胚层和外胚层组织分化的性腺生殖细胞。向这些细胞系中加入成骨细胞分化的补充物，包括BMP-2，增加了钙化面积，这可通过von Kossa染色证实，并显示上清液中碱性磷酸酶升高;这些是成骨细胞分化的指标。2.成脂细胞分化：添加用于成脂细胞分化的补充剂，包括吲哚美辛、地塞米松和胰岛素，增加了细胞质中具有油红O-脂质的细胞数量。3.肌纤维母细胞分化：TGF-β1（一种纤维化疾病中的纤维化因子）处理后，对α-平滑肌肌动蛋白（α-SMA）免疫反应的细胞数量增加，Western blotting证实了这种增加。这些研究部分阐明了间充质分化的机制，这些细胞系将为研究间充质分化的机制提供有用的材料。6.此外，从大鼠皮下组织中产生的恶性纤维组织细胞瘤中建立了一个新的细胞系，显示了组织细胞的性质，另一个细胞系从子宫颈产生的恶性神经鞘瘤中分离。这些细胞系也将成为研究间充质分化的有益工具。

项目成果

Yamate, J., et al.: "Characterization of newly-established tumor lines from a spontaneous malignat schwannoma in F344 rats : nerve growth factor production, growth inhibition by transforming growth factor-βi, and macrophage-like phenotype expression."Acta

Yamate, J. 等人：“F344 大鼠自发性恶性神经鞘瘤新建立的肿瘤系的特征：神经生长因子的产生、转化生长因子-βi 的生长抑制以及巨噬细胞样表型表达。”Acta

Yamate, J., et al.: "Tumor lines from a spontaneous rat endometrial stromal sarcoma, showing dendritic cell- and myofibroblastic cell-like phenotypes."J.Comp.Pathol.. (in press). (2004)

Yamate, J. 等人：“来自自发性大鼠子宫内膜间质肉瘤的肿瘤系，显示树突状细胞和肌纤维母细胞样表型。”J.Comp.Pathol..（出版中）。

Tumor lines from a spontaneous rat endometrial stromal sarcoma, showing dendritic cell- and myofibroblastic cell-like phenotypes.

来自自发性大鼠子宫内膜间质肉瘤的肿瘤系，显示树突状细胞和肌纤维母细胞样表型。

• 发表时间: 2004
• 期刊: J Comp Pathol 131
• 作者: C.J.Kasanga;C.J.Kasanga et al.;Yamate J et al.
• 通讯作者: Yamate J et al.