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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Podrobná bibliografia
Vydané v:	Nature communications Ročník 8; číslo 1; s. 15613 - 17
Hlavní autori:	Quarta, Marco, Cromie, Melinda, Chacon, Robert, Blonigan, Justin, Garcia, Victor, Akimenko, Igor, Hamer, Mark, Paine, Patrick, Stok, Merel, Shrager, Joseph B., Rando, Thomas A.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 20.06.2017 Nature Publishing Group Nature Portfolio
Predmet:	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
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/ncomms15613