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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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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. |
format | Online Article Text |
id | pubmed-5057287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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