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

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:
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
项目状态:
已结题
起止时间:
2002 至 2003

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中文摘要
翻译
最近,分化。在骨髓移植后,不仅在小鼠身上,而且在人类身上,包括骨骼肌组织,都证实了除了造血细胞以外的其他血统的起源。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。骨髓中,2)骨髓干细胞的可塑性。此外,两种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,这三种可能性之间的主要贡献机制尚不清楚。本课题旨在分析GFP转基因小鼠骨髓细胞移植后骨髓细胞向骨骼肌组织转分化的机制。转化为受照射的正常成年小鼠或c-kit突变的W/W小鼠。此外,在体外培养体系中,我们拟建立具有向骨骼肌分化潜能的细胞系。首先,将GFP标记的KSL细胞移植后,我们可以很容易地检测到y GFP表达的骨骼肌。GFP的表达逐渐减少,30d后逐渐消失。然而,从移植的小鼠的单个肌肉纤维培养中发现了GFP的表达,这表明移植的KSL细胞已经转化为具有干细胞特征的卫星面纱。另一方面,我们现在正在研究具有向骨骼肌组织分化潜能的细胞系。
英文摘要
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.
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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》。
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Hiramatsu, H., Nishikomori, R., Heike, T., Ito, M., Kobayashi, K., Katamura, K., Nakahata, T.: "Complete reconstitution of human lymphocytes drom cord blood CD34+ cells using the NOD/SCID/γc^<null> mice model"Blood. 102. 873-880 (2003)
Hiramatsu, H.、Nishikomori, R.、Heike, T.、Ito, M.、Kobayashi, K.、Katamura, K.、Nakahata, T.:“使用 NOD/ 完全重建人淋巴细胞从脐带血 CD34+ 细胞SCID/γc^<null>小鼠模型“Blood. 102. 873-880 (2003)
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25
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