Wnt7a stimulates myogenic stem cell motility and engraftment resulting in improved muscle strength
Autor: | C. Florian Bentzinger, Danny A. Stark, Nicolas A. Dumont, Yu Xin Wang, Jérôme Frenette, Kevin Nhan, Julia von Maltzahn, Michael A. Rudnicki, D.D.W. Cornelison |
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Rok vydání: | 2014 |
Předmět: |
rac1 GTP-Binding Protein
medicine.medical_treatment Dishevelled Proteins Muscular Dystrophies Receptors G-Protein-Coupled Cell Fusion Mice Cell Movement Genes Reporter Cell polarity Myocyte Promoter Regions Genetic Research Articles Mice Knockout Cell Polarity PAX7 Transcription Factor Stem-cell therapy Endocytosis 3. Good health Cell biology medicine.anatomical_structure Stem cell Signal Transduction Myoblasts Skeletal Recombinant Fusion Proteins Green Fluorescent Proteins Mice Transgenic Biology Article Cell Line medicine Animals Humans Muscle Strength Progenitor cell Muscle Skeletal Protein kinase B PI3K/AKT/mTOR pathway Adaptor Proteins Signal Transducing Neuropeptides Skeletal muscle Hypertrophy Cell Biology Phosphoproteins Molecular biology Frizzled Receptors Wnt Proteins Disease Models Animal Luminescent Proteins Mice Inbred mdx |
Zdroj: | The Journal of cell biology The Journal of Cell Biology |
ISSN: | 1540-8140 0021-9525 |
Popis: | In addition to stimulating skeletal muscle growth and repair, Wnt7a/Fzd7 signaling increases the polarity and directional migration of myogenic progenitors and improves the efficacy of muscle stem cell therapy. 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. |
Databáze: | OpenAIRE |
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