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胚外中胚层来源的细胞在杜兴氏肌营养不良症的 mdx 模型中赋予人抗肌萎缩蛋白。

Cells of extraembryonic mesodermal origin confer human dystrophin in the mdx model of Duchenne muscular dystrophy.

机构信息

Department of Reproductive Biology, National Institute for Child Health and Development, Tokyo, Japan.

出版信息

J Cell Physiol. 2010 Jun;223(3):695-702. doi: 10.1002/jcp.22076.

DOI:10.1002/jcp.22076
PMID:20162617
Abstract

Duchenne muscular dystrophy is an X-linked recessive genetic disease characterized by severe skeletal muscular degeneration. The placenta is considered to be a promising candidate cell source for cellular therapeutics because it contains a large number of cells and heterogenous cell populations with myogenic potentials. We analyzed the myogenic potential of cells obtained from six parts of the placenta, that is, umbilical cord, amniotic epithelium, amniotic mesoderm, chorionic plate, villous chorion, and decidua basalis. In vitro cells derived from amniotic mesoderm, chorionic plate, and villous chorion efficiently transdifferentiate into myotubes. In addition, in vivo implantation of placenta-derived cells into dystrophic muscles of immunodeficient mdx mice restored sarcolemmal expression of human dystrophin. Differential contribution to myogenesis in this study may be attributed to placental portion-dependent default cell state. Molecular taxonomic characterization of placenta-derived maternal and fetal cells in vitro will help determine the feasibility of cell-based therapy.

摘要

杜氏肌营养不良症是一种 X 连锁隐性遗传疾病,其特征是严重的骨骼肌肉退化。胎盘被认为是细胞治疗有前途的候选细胞来源,因为它含有大量具有成肌潜能的细胞和异质细胞群体。我们分析了来自胎盘六个部分的细胞的成肌潜能,即脐带、羊膜上皮、羊膜中胚层、胎盘绒毛板、绒毛膜和底蜕膜。体外来源于羊膜中胚层、胎盘绒毛板和绒毛膜的细胞可有效转分化为肌管。此外,将胎盘来源的细胞体内植入免疫缺陷 mdx 小鼠的肌肉营养不良症肌肉中可恢复人源抗肌萎缩蛋白的肌膜表达。本研究中分化对成肌的不同贡献可能归因于胎盘部位依赖的默认细胞状态。体外胎盘源性母胎细胞的分子分类特征将有助于确定基于细胞的治疗的可行性。

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