Basic study for regenerative medicine in muscular dystrophy by bone marrow transplantation

骨髓移植再生医学治疗肌营养不良症的基础研究

• 批准号: 16590856
• 负责人: HAGIWARA Hiroki
• 金额: $ 2.3万
• 依托单位: Kawasaki Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590856/
• 关键词: bone marrow transplantation; muscular dystrophy; regenerative medicine; EGFP mouse; dy mouse; mdx moude; extracellular matrix; laminin

To evaluate the therapeutic potential of bone marrow, we examined whether pathogenesis in dystrophin-deficient (mdx) mice (a model for Duchenne muscular dystrophy [DMD]) and laminin alpha2-deficient (dy) mice (a model for congenital muscular dystrophy type 1A [MDC1A]) is ameliorated by bone marrow transplantation. We selected whole bone marrow cells for transplantation. Green fluorescent protein (GFP) mice were used as donors. Both model mice exhibited GFP-positive muscle fibers. In mdx mice, bone marrow transplantation failed to produce any significant differences in muscle pathology, although some GFP-positive fibers with restored dystrophin expression were observed. In contrast, in the dy mice, bone marrow transplantation led to a significant increase in lifespan and an increase in growth rate, muscle strength, and respiratory function. We conclude that bone marrow transplantation improved outcome in dy mice but not mdx mice. It is possible that bone marrow transplantation therapies designed to ameliorate muscular dystrophies are more likely to succeed in MDC1A than in DMD. Our results would open up the direct clinical application of bone marrow transplantation for muscular dystrophies such as MDC1A.

为了评估骨髓的治疗潜力，我们检查了骨髓移植是否改善了肌营养不良蛋白缺陷型（mdx）小鼠（Duchenne肌营养不良[DMD]的模型）和层粘连蛋白α 2缺陷型（dy）小鼠（先天性肌营养不良1A型[MDC 1A]的模型）的发病机制。我们选择全骨髓细胞进行移植。使用绿色荧光蛋白（GFP）小鼠作为供体。两种模型小鼠均表现出GFP阳性肌纤维。在mdx小鼠中，骨髓移植未能产生任何显着的差异，肌肉病理学，虽然一些GFP阳性纤维与恢复肌营养不良蛋白的表达进行了观察。相反，在dy小鼠中，骨髓移植导致寿命显著延长，生长速度、肌肉力量和呼吸功能增加。我们的结论是骨髓移植改善了dy小鼠的预后，但对mdx小鼠没有改善。旨在改善肌营养不良症的骨髓移植疗法在MDC1A中比在DMD中更有可能成功。我们的研究结果将开辟骨髓移植治疗肌营养不良症（如MDC1A）的直接临床应用。

项目成果

筋ジストロフィーモデルマウスに対する骨髄移植法の治療効果の検討

骨髓移植对肌营养不良模型小鼠的治疗效果考察

• 发表时间: 2005
• 期刊: 臨床神経学 45
• 作者: Iguchi Y;Hoshi Y;Tanosaki M;Taira M;Hashimoto I.;萩原宏毅
• 通讯作者: 萩原宏毅

新しいジストロフィン結合蛋白複合体の細胞外リガンド-バイグリカン

新型肌营养不良蛋白结合蛋白复合物的胞外配体 - 双糖链蛋白聚糖

• 发表时间: 2004
• 期刊: 臨床神経学 44
• 作者: Kamo;I.;Tomoyasu;H.;Yamamoto;T.;Kusakabe;M.;Kikuchi;A.;萩原宏毅
• 通讯作者: 萩原宏毅

Skeletal muscle hyperplasia in the transgenic mice overexpressing the myostatin prodomain

过度表达肌生长抑制素前结构域的转基因小鼠骨骼肌增生

• 发表时间: 2004
• 期刊: Neuromuscular Disorders 14(8-9)
• 作者: ShogoMatsumoto;Yoshihisa Kitamura;Hiroshi Mori et al.;Hagiwara H
• 通讯作者: Hagiwara H

Restoration of a myopathic phenotype of mutant caveolin-3 transgenic mice by crossing with mutant myostatin transgenic mice.

通过与突变型肌生长抑制素转基因小鼠杂交恢复突变型 Caveolin-3 转基因小鼠的肌病表型。

• 发表时间: 2004
• 期刊: Neuromuscular Disorders 14(8-9)
• 作者: Ohsawa Y;Hagiwara H;Sasano S;Nishi N;Yasue A;Noji S;Sunada Y.
• 通讯作者: Sunada Y.

Restoration of a myopathic phenotype of mutant caveolin-3 transgenic mice by crossing with mutant myostatin transgenic mice

通过与突变肌生长抑制素转基因小鼠杂交恢复突变型caveolin-3转基因小鼠的肌病表型

• 发表时间: 2004
• 期刊: Neuromuscular Disorders 14(8-9)
• 作者: Nishioka K;Mizoguchi K;et al.;Ohasawa Y
• 通讯作者: Ohasawa Y