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A human in vitro model of Duchenne muscular dystrophy muscle formation and contractility

Tongue weakness, like all weakness in Duchenne muscular dystrophy (DMD), occurs as a result of contraction-induced muscle damage and deficient muscular repair. Although membrane fragility is known to potentiate injury in DMD, whether muscle stem cells are implicated in deficient muscular repair rema...

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Autores principales: Nesmith, Alexander P., Wagner, Matthew A., Pasqualini, Francesco S., O’Connor, Blakely B., Pincus, Mark J., August, Paul R., Parker, Kevin Kit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5057287/
https://www.ncbi.nlm.nih.gov/pubmed/27697929
http://dx.doi.org/10.1083/jcb.201603111
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author Nesmith, Alexander P.
Wagner, Matthew A.
Pasqualini, Francesco S.
O’Connor, Blakely B.
Pincus, Mark J.
August, Paul R.
Parker, Kevin Kit
author_facet Nesmith, Alexander P.
Wagner, Matthew A.
Pasqualini, Francesco S.
O’Connor, Blakely B.
Pincus, Mark J.
August, Paul R.
Parker, Kevin Kit
author_sort Nesmith, Alexander P.
collection PubMed
description Tongue weakness, like all weakness in Duchenne muscular dystrophy (DMD), occurs as a result of contraction-induced muscle damage and deficient muscular repair. Although membrane fragility is known to potentiate injury in DMD, whether muscle stem cells are implicated in deficient muscular repair remains unclear. We hypothesized that DMD myoblasts are less sensitive to cues in the extracellular matrix designed to potentiate structure–function relationships of healthy muscle. To test this hypothesis, we drew inspiration from the tongue and engineered contractile human muscle tissues on thin films. On this platform, DMD myoblasts formed fewer and smaller myotubes and exhibited impaired polarization of the cell nucleus and contractile cytoskeleton when compared with healthy cells. These structural aberrations were reflected in their functional behavior, as engineered tongues from DMD myoblasts failed to achieve the same contractile strength as healthy tongue structures. These data suggest that dystrophic muscle may fail to organize with respect to extracellular cues necessary to potentiate adaptive growth and remodeling.
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spelling pubmed-50572872017-04-10 A human in vitro model of Duchenne muscular dystrophy muscle formation and contractility Nesmith, Alexander P. Wagner, Matthew A. Pasqualini, Francesco S. O’Connor, Blakely B. Pincus, Mark J. August, Paul R. Parker, Kevin Kit J Cell Biol Research Articles Tongue weakness, like all weakness in Duchenne muscular dystrophy (DMD), occurs as a result of contraction-induced muscle damage and deficient muscular repair. Although membrane fragility is known to potentiate injury in DMD, whether muscle stem cells are implicated in deficient muscular repair remains unclear. We hypothesized that DMD myoblasts are less sensitive to cues in the extracellular matrix designed to potentiate structure–function relationships of healthy muscle. To test this hypothesis, we drew inspiration from the tongue and engineered contractile human muscle tissues on thin films. On this platform, DMD myoblasts formed fewer and smaller myotubes and exhibited impaired polarization of the cell nucleus and contractile cytoskeleton when compared with healthy cells. These structural aberrations were reflected in their functional behavior, as engineered tongues from DMD myoblasts failed to achieve the same contractile strength as healthy tongue structures. These data suggest that dystrophic muscle may fail to organize with respect to extracellular cues necessary to potentiate adaptive growth and remodeling. The Rockefeller University Press 2016-10-10 /pmc/articles/PMC5057287/ /pubmed/27697929 http://dx.doi.org/10.1083/jcb.201603111 Text en © 2016 Nesmith et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Nesmith, Alexander P.
Wagner, Matthew A.
Pasqualini, Francesco S.
O’Connor, Blakely B.
Pincus, Mark J.
August, Paul R.
Parker, Kevin Kit
A human in vitro model of Duchenne muscular dystrophy muscle formation and contractility
title A human in vitro model of Duchenne muscular dystrophy muscle formation and contractility
title_full A human in vitro model of Duchenne muscular dystrophy muscle formation and contractility
title_fullStr A human in vitro model of Duchenne muscular dystrophy muscle formation and contractility
title_full_unstemmed A human in vitro model of Duchenne muscular dystrophy muscle formation and contractility
title_short A human in vitro model of Duchenne muscular dystrophy muscle formation and contractility
title_sort human in vitro model of duchenne muscular dystrophy muscle formation and contractility
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5057287/
https://www.ncbi.nlm.nih.gov/pubmed/27697929
http://dx.doi.org/10.1083/jcb.201603111
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