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MBC in Press, published online ahead of print February 21, 2007
Mol. Biol. Cell 10.1091/mbc.E06-09-0872

A more recent version of this article appeared on May 1, 2007
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Submitted on September 28, 2006
Revised on January 19, 2007
Accepted on February 6, 2007

Menstrual Blood-derived Cells Confer Human Dystrophin Expression in the Murine Model of Duchenne Muscular Dystrophy via Cell Fusion and Myogenic Transdifferentiation

ChangHao Cui,*{dagger} Taro Uyama,* Kenji Miyado,* Masanori Terai,* Satoru Kyo,{ddagger} Tohru Kiyono,{sect} and Akihiro Umezawa*

*Department of Reproductive Biology and Pathology, National Institute for Child Health and Development, Tokyo, 157-8567, Japan; {dagger}Department of Basic Medical Science, Mudanjiang Medical College, Mudanjiang, 157011, China; {ddagger}Department of Obstetrics and Gynecology, Kanazawa University, School of Medicine, Kanazawa, 920-8640, Japan; {sect}Virology Division, National Cancer Center Research Institute, Tokyo, 104-0045, Japan

Monitoring Editor: M. Bishr Omary

Duchenne muscular dystrophy, 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 duchenne muscular dystrophy. 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 EGFP 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 at a high frequency through cell fusion and transdifferentiation in vitro and in vivo.


Address correspondence to: Akihiro Umezawa (umezawa{at}1985.jukuin.keio.ac.jp)







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