Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy via cell fusion and myogenic transdifferentiation
Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy via cell fusion and myogenic transdifferentiation
复制标题
DOI：
10.1091/mbc.e06-09-0872
复制
发表时间：
2007-05-01
影响因子：
3.3
通讯作者：
Umezawa, Akihiro
中科院分区：
文献类型：
--
作者：
Cui, Chang-Hao;Uyama, Taro;Umezawa, Akihiro
Duchenne肌营养不良症是儿童最常见的致死性遗传病，是一种X连锁的隐性肌肉疾病，其特征是肌纤维的肌膜上缺乏抗肌营养不良蛋白。我们检查了从子宫内膜组织样本中获得的假定的子宫内膜前体细胞，以确定这些细胞是否修复了DMD小鼠MDX模型中的肌肉退行性变。移植的细胞在免疫缺陷的mdx小鼠退化的肌肉中赋予了人肌营养不良蛋白。然后，我们检查了月经血源性细胞，以确定原代培养的未转化细胞是否也修复了营养不良的肌肉。在体内，将月经血源性细胞转移到免疫缺陷的MDX小鼠营养不良的肌肉中，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标记移植细胞，以及人和小鼠细胞核的差异染色表明，人类dystrophin的表达是由于宿主肌细胞和移植细胞之间的细胞融合。体外分析表明，子宫内膜祖细胞和月经血源性细胞可以高效地转分化为成肌细胞/肌细胞，通过体外共培养与C2C12小鼠成肌细胞融合，融合后开始表达dystrophin。这些结果表明，在体内外，子宫内膜祖细胞和月经血源性细胞可以通过细胞融合和转分化将dystrophin转移到营养不良的心肌细胞。
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 endometrial progenitor obtained from endometrial 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 menstrual blood-derived cells to determine whether primarily cultured nontransformed cells also repair dystrophied muscle. In vivo transfer of menstrual blood-derived 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 endometrial progenitor cells and menstrual blood-derived 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 progenitor cells and menstrual blood-derived cells can transfer dystrophin into dystrophied myocytes through cell fusion and transdifferentiation in vitro and in vivo.