Wnt7a stimulates myogenic stem cell motility and engraftment resulting in improved muscle strength |
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| Authors: | Alexander Braun Kyvan Dang Felinah Buslig Michelle A Baird Michael W Davidson Clare M Waterman Kenneth A Myers |
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| Institution: | 1.Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada;2.Faculty of Medicine, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada;3.Division of Biological Sciences, and 4.Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211;5.Faculty of Medicine, Department of Rehabilitation, Laval University, Quebec City, QC G1V 4G2, Canada |
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| Abstract: | 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 Dvl2 and the small GTPase Rac1. 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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