Development of therapeutic strategy for Duchenne muscular dystrophy-Based on cell fusion and myogenic transdifferentiation theory

杜氏肌营养不良症治疗策略的制定——基于细胞融合和肌源性转分化理论

• 批准号: 19790749
• 负责人: SAI Syoko
• 金额: $ 2.47万
• 依托单位: National Research Institute for Child Health and Development
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19790749/
• 关键词: 筋ジストロフィー; 周産期幹細胞; 幹細胞; 骨格筋; 細胞移植; 筋ジストロフー

Duchenne muscular dystrophy (DMD), the most common lethal genetic disorder in children, is an X-linked recessive muscle disease characterized by the absence of dystrophin at the sarcolemma of muscle fibers. We examined a putative mesenchymal stromal cells obtained from endometrial or placenta tissue samples to determine whether these cells repair muscular degeneration in a murine mdx model of DMD. Implanted cells conferred human dystrophin in degenerated muscle of immunodeficient mdx mice. We then examined endometrial-derived cells, menstrual blood-derived cells, and placenta-derived cell to determine whether primarily cultured nontransformed cells also repair dystrophied muscle. In vivo transfer of these cells into dystrophic muscles of immunodeficient mdx mice restored sarcolemmal expression of dystrophin. Labeling of implanted cells with enhanced green fluorescent protein and differential staining of human and murine nuclei suggest that human dystrophin expression is due to cell fusion between host myocytes and implanted cells. In vitro analysis revealed that cells can efficiently transdifferentiate into myoblasts/myocytes, fuse to C2C12 murine myoblasts by in vitro coculturing, and start to express dystrophin after fusion. These results demonstrate that the endometrial-derived cells, menstrual blood-derived cells, and placenta-derived cell can transfer dystrophin into dystrophied myocytes through cell fusion and transdifferentiation in vitro and in vivo.

Duchenne肌肉营养不良（DMD）是儿童中最常见的致命遗传疾病，是一种X连锁的隐性肌肉疾病，其特征是在肌肉纤维的肌肉中缺乏肌营养不良蛋白。我们检查了从子宫内膜或胎盘组织样品获得的假定的间充质基质细胞，以确定这些细胞在DMD的鼠MDX模型中是否修复了肌肉变性。植入的细胞赋予人肌营养不良蛋白在免疫缺陷的MDX小鼠的退化肌肉中。然后，我们检查了子宫内膜衍生的细胞，月经衍生的细胞和胎盘衍生的细胞，以确定主要培养的非转化细胞是否还可以修复营养不良的肌肉。这些细胞在体内转移到免疫缺陷的MDX小鼠的营养不良肌肉中，恢复了肌营养不良蛋白的肌膜表达。用增强的绿色荧光蛋白和人和鼠核的差异染色的植入细胞的标记表明，人肌营养不良蛋白的表达是由于宿主肌细胞和植入细胞之间的细胞融合所致。体外分析表明，细胞可以有效地转化为肌细胞/成肌细胞，通过体外共培养融合到C2C12鼠肌细胞，并在融合后开始表达肌营养不良蛋白。这些结果表明，子宫内膜衍生的细胞，月经衍生的细胞和胎盘衍生的细胞可以通过细胞融合和体外和体内通过细胞融合和转分化的细胞融合和转分化转移肌营养不良的肌细胞。

项目成果

Myogenic transdifferentiation of menstrual blood-derived cells.

• 发表时间: 2007-12
• 期刊: Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology
• 作者: M. Toyoda;Changyi Cui;A. Umezawa

Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells

• DOI: 10.1634/stemcells.2007-0826
• 发表时间: 2008-01-01
• 期刊: STEM CELLS
• 影响因子: 5.2
• 作者: Hida, Naoko;Nishiyama, Nobuhiro;Umezawa, Akihiro
• 通讯作者: Umezawa, Akihiro

'Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells

• DOI: 10.1016/j.yexcr.2007.04.028
• 发表时间: 2007-07-15
• 期刊: EXPERIMENTAL CELL RESEARCH
• 影响因子: 3.7
• 作者: Okamoto, Kazuma;Miyoshi, Shunichiro;Umezawa, Akihiro
• 通讯作者: Umezawa, Akihiro

Cells of Extraembryonic Mesodermal Origin Confer Human Dystrophin in the Mdx Model of Duchenne Muscular Dystrophy

• DOI: 10.1002/jcp.22076
• 发表时间: 2010-06-01
• 期刊: JOURNAL OF CELLULAR PHYSIOLOGY
• 影响因子: 5.6
• 作者: Kawamichi, Yayoi;Cui, Chang-Hao;Umezawa, Akihiro
• 通讯作者: Umezawa, Akihiro

Myogenesis by Endometrium derived Cells.

子宫内膜衍生细胞的肌生成。

• 发表时间: 2007
• 期刊: Medical Technology. 35
• 作者: Cui CH;Umezawa A.
• 通讯作者: Umezawa A.