期刊
JOURNAL OF CELL BIOLOGY
卷 205, 期 1, 页码 97-111出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201310035
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资金
- Swiss National Science Foundation
- QEII-GSST
- Canadian Institutes of Health Research
- Muscular Dystrophy Association
- National Institutes of Health
- Canadian Stem Cell Network
- Ontario Ministry of Research and Innovation
- Canada Research Chair Program
Wnt7a/Fzd7 signaling stimulates skeletal muscle growth and repair by inducing the symmetric expansion of satellite stem cells through the planar cell polarity pathway and by activating the Akt/mTOR growth pathway in muscle fibers. Here we describe a third level of activity where Wnt7a/Fzd7 increases the polarity and directional migration of mouse satellite cells and human myogenic progenitors through activation of DvI2 and the small GTPase Racl. Importantly, these effects can be exploited to potentiate the outcome of myogenic cell transplantation into dystrophic muscles. We observed that a short Wnt7a treatment markedly stimulated tissue dispersal and engraftment, leading to significantly improved muscle function. Moreover, myofibers at distal sites that fused with Wnt7a-treated cells were hypertrophic, suggesting that the transplanted cells deliver activated Wnt7a/Fzd7 signaling complexes to recipient myofibers. Taken together, we describe a viable and effective ex vivo cell modulation process that profoundly enhances the efficacy of stem cell therapy for skeletal muscle.
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