Bioengineered constructs combined with exercise enhance stem cell-mediated treatment of volumetric muscle loss

Volumetric muscle loss (VML) is associated with loss of skeletal muscle function, and current treatments show limited efficacy. Here we show that bioconstructs suffused with genetically-labelled muscle stem cells (MuSCs) and other muscle resident cells (MRCs) are effective to treat VML injuries in m...

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Bibliographic Details
Published in:Nature communications Vol. 8; no. 1; pp. 15613 - 17
Main Authors: Quarta, Marco, Cromie, Melinda, Chacon, Robert, Blonigan, Justin, Garcia, Victor, Akimenko, Igor, Hamer, Mark, Paine, Patrick, Stok, Merel, Shrager, Joseph B., Rando, Thomas A.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 20.06.2017
Nature Publishing Group
Nature Portfolio
Subjects:
13/100
13/107
631/532/2439
631/61/2035
692/698/1671/1668/1973
Aged
Animal models
Animals
Bioengineering
Bioreactors
Cell culture
Cell- and Tissue-Based Therapy - methods
Damage
Effectiveness
Exercise - physiology
Female
Functional anatomy
Humanities and Social Sciences
Humans
Imaging
Implantation
Injuries
Injury analysis
Injury prevention
Innervation
Male
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Middle Aged
multidisciplinary
Muscle contraction
Muscle function
Muscle, Skeletal - injuries
Muscle, Skeletal - pathology
Muscle, Skeletal - transplantation
Muscles
Physical training
Regeneration
Restoration
Science
Science (multidisciplinary)
Skeletal muscle
Skeleton
Stem cell transplantation
Stem Cell Transplantation - methods
Stem cells
Surgical implants
Survival
Tissue Engineering - methods
Tissue Scaffolds
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Volumetric muscle loss (VML) is associated with loss of skeletal muscle function, and current treatments show limited efficacy. Here we show that bioconstructs suffused with genetically-labelled muscle stem cells (MuSCs) and other muscle resident cells (MRCs) are effective to treat VML injuries in mice. Imaging of bioconstructs implanted in damaged muscles indicates MuSCs survival and growth, and ex vivo analyses show force restoration of treated muscles. Histological analysis highlights myofibre formation, neovascularisation, but insufficient innervation. Both innervation and in vivo force production are enhanced when implantation of bioconstructs is followed by an exercise regimen. Significant improvements are also observed when bioconstructs are used to treat chronic VML injury models. Finally, we demonstrate that bioconstructs made with human MuSCs and MRCs can generate functional muscle tissue in our VML model. These data suggest that stem cell-based therapies aimed to engineer tissue in vivo may be effective to treat acute and chronic VML. Volumetric muscle loss leads to functional muscle impairment, and current stem cell-based treatments show limited efficacy. Here, the authors generate a stem cell scaffold, implant it in mice, and show that an exercise regimen enhances innervation and restoration of muscle function in mice.
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ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms15613