ESTABLISHMENT OF FUNDAMENTAL STRATEGIES FOR SKELETAL MUSCLE TISSUE REGENERAIZON USING HEMATOPOIETIC CELLS FOR MUSCULAR DYSTROPHY DISEASE

建立利用造血细胞治疗肌营养不良症的骨骼肌组织再生的基本策略

• 批准号: 14370246
• 负责人: HEIKE Toshio
• 金额: $ 8.13万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370246/
• 关键词: hematopoietic stem cell; skeletal muscle; plasticity; irradiation; c-kit; satellite cell; 筋ジストロフィー症; 骨髄細胞; 幹細胞; GFP; single fiber culture; ラミニン

Recently, the differentiation. into other lineages than hematopoietic origein was confirmed after bone marrow transplantation not only in mice but also in humans, including skeletal muscle tissue. This observation imply the following two possibilities; 1) the presence of pluripotent stem cells. in bone marrow, 2) the plasticity of bone marrow stem cells. Otherwise, the fusion of two kinds of cells with different characteristics was proposed to be the cause of this transdifferentiation. In the case of the transdifferentiation into skeletal muscle, the major contribution mechanism among these three possibilities is obscure. In this project, -we intended to analyze the mechanism four the transdifferentiation of bone, marrow cells into skeletal muscle tissue after the transplantation of bone marrow cells from GFP transgenic mice. into irradiated normal adult mice or W/W mice with c-kit mutation. In addition, in vitro system, we intended to establish, the cell line with the differentiation potential into skeletal muscle. First, after transplanting the KSL cells with GFP labeling, we could easily detect the skeletal muscle with y GFP expression. This GFP expression decreased gradually and faded out after 30 days. However, the culture of single muscle fiber from this transplanted mice revealed the expression with GFP expression, indicating the conversion into satellite veils with stem cell characteristics from transplanted KSL cells. On the other hand, we are now in the way to characterize the cell line with differentiation potential into skeletal muscle tissue.

最近，分化。不仅在小鼠身上，而且在人类身上，包括骨骼肌组织的骨髓移植后，都证实了除了造血起源之外的其他谱系。这一观察结果意味着以下两种可能性； 1）多能干细胞的存在。在骨髓中，2）骨髓干细胞的可塑性。另外，两种具有不同特性的细胞的融合被认为是这种转分化的原因。在转分化为骨骼肌的情况下，这三种可能性中的主要贡献机制尚不清楚。在本项目中，我们打算分析GFP转基因小鼠骨髓细胞移植后骨、骨髓细胞转分化为骨骼肌组织的机制四。进入受辐射的正常成年小鼠或带有 c-kit 突变的 W/W 小鼠。此外，在体外系统中，我们打算建立具有分化成骨骼肌潜力的细胞系。首先，移植带有 GFP 标记的 KSL 细胞后，我们可以轻松检测到 y GFP 表达的骨骼肌。该 GFP 表达逐渐减少，并在 30 天后消失。然而，来自该移植小鼠的单肌纤维培养物显示出 GFP 表达，表明移植的 KSL 细胞转化为具有干细胞特征的卫星膜。另一方面，我们现在正在研究具有分化成骨骼肌组织潜力的细胞系的特征。

项目成果

Xu, Y., Arai, H., Sario, H., Murayama, T., Yoshimoto, M., Heike, T., Nakahata, T., Nishikawa, S., Kita, T., Yokode, M.: "Role of bone marrow-derived progenitor cells in cuff-induced vascular injury in mice"Arteriosclerosis, Thrombosis, and Vascular Biolog

Xu, Y.、Arai, H.、Sario, H.、Murayama, T.、Yoshimoto, M.、Heike, T.、Nakahata, T.、Nishikawa, S.、Kita, T.、Yokode, M.：

Nishikomori, R., Akutagawa, H., Maruyama, K., Nakata-Hizume, M., Ohmori, K., Mizuno, A., Yasumi, T., Kus unoki, T., Hei ke, T., Nakahata, T.: "X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role

西小森 R.、芥川 H.、丸山 K.、中田 Hizume, M.、大森 K.、水野 A.、康美 T.、Kus unoki, T.、Hei ke, T.、中畑

Heike T et al.: "Ex vivo expansion of hematopoietic stem cells by cytokines"Biochemica et Biophysica Acta. 199 2. 313-321 (2002)

Heike T 等人：“细胞因子对造血干细胞的体外扩增”《生物化学与生物物理学学报》。

Xu, Y.et al.: "Role of bone marrow-derived progenitor cells in cuff-induced vascular injury in mice"Arteriosclerosis, Thrombosis, and Vascular Biology. (in press).

Xu, Y.等人：“骨髓来源的祖细胞在袖带诱导的小鼠血管损伤中的作用”动脉硬化、血栓形成和血管生物学。

Nishikomori, R. et al.: "X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development/or survival"Blood. (in press).

Nishikomori, R. 等人：“由 NEMO 逆转镶嵌引起的 X 连锁外胚层发育不良和免疫缺陷揭示了 NEMO 在人类 T 细胞发育/或存活中的关键作用”。