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
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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