Bioengineered constructs combined with exercise enhance stem cell-mediated treatment of volumetric muscle loss
Marco Quarta (),
Melinda Cromie,
Robert Chacon,
Justin Blonigan,
Victor Garcia,
Igor Akimenko,
Mark Hamer,
Patrick Paine,
Merel Stok,
Joseph B. Shrager and
Thomas A. Rando ()
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Marco Quarta: Stanford University School of Medicine
Melinda Cromie: Stanford University School of Medicine
Robert Chacon: Stanford University School of Medicine
Justin Blonigan: Stanford University School of Medicine
Victor Garcia: Stanford University School of Medicine
Igor Akimenko: Stanford University School of Medicine
Mark Hamer: Stanford University School of Medicine
Patrick Paine: Stanford University School of Medicine
Merel Stok: Erasmus Medical Center
Joseph B. Shrager: Stanford University School of Medicine and VA Palo Alto Health Care System
Thomas A. Rando: Stanford University School of Medicine
Nature Communications, 2017, vol. 8, issue 1, 1-17
Abstract:
Abstract 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.
Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15613
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DOI: 10.1038/ncomms15613
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