title: A human in vitro model of Duchenne muscular dystrophy muscle formation and contractility.
abstract: 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.
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering and Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors.forename: Alexander P
authors.identifier: http://orcid.org/0000-0003-2881-9002
authors.initials: AP
authors.lastname: Nesmith
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering and Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Wagner
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering and Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors.forename: Francesco S
authors.identifier: http://orcid.org/0000-0001-7038-3121
authors.initials: FS
authors.lastname: Pasqualini
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering and Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors.forename: Blakely B
authors.identifier: http://orcid.org/0000-0003-0636-9514
authors.initials: BB
authors.lastname: O'Connor
authors.affiliation: Sanofi U.S.-Tucson Innovation Center, Oro Valley, AZ 85755.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pincus
authors.affiliation: Sanofi U.S.-Tucson Innovation Center, Oro Valley, AZ 85755.
authors.forename: Paul R
authors.identifier: http://orcid.org/0000-0003-2601-2379
authors.initials: PR
authors.lastname: August
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering and Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138 kkparker@seas.harvard.edu.
authors.forename: Kevin Kit
authors.initials: KK
authors.lastname: Parker
mesh_terms: D000199:Actins / Q000378:metabolism; D016880:Anisotropy; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D053144:Cell Nucleus Shape; D002675:Child, Preschool; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology* / Q000503:physiopathology*; D032446:Myoblasts / Q000473:pathology; D023822:Tissue Engineering; D014059:Tongue
chemical_list: D000199:Actins