Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs.

Published

Journal Article

Existing in vitro models of human skeletal muscle cannot recapitulate the organization and function of native muscle, limiting their use in physiological and pharmacological studies. Here, we demonstrate engineering of electrically and chemically responsive, contractile human muscle tissues ('myobundles') using primary myogenic cells. These biomimetic constructs exhibit aligned architecture, multinucleated and striated myofibers, and a Pax7(+) cell pool. They contract spontaneously and respond to electrical stimuli with twitch and tetanic contractions. Positive correlation between contractile force and GCaMP6-reported calcium responses enables non-invasive tracking of myobundle function and drug response. During culture, myobundles maintain functional acetylcholine receptors and structurally and functionally mature, evidenced by increased myofiber diameter and improved calcium handling and contractile strength. In response to diversely acting drugs, myobundles undergo dose-dependent hypertrophy or toxic myopathy similar to clinical outcomes. Human myobundles provide an enabling platform for predictive drug and toxicology screening and development of novel therapeutics for muscle-related disorders.

Full Text

Duke Authors

Cited Authors

  • Madden, L; Juhas, M; Kraus, WE; Truskey, GA; Bursac, N

Published Date

  • January 9, 2015

Published In

Volume / Issue

  • 4 /

Start / End Page

  • e04885 -

PubMed ID

  • 25575180

Pubmed Central ID

  • 25575180

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

International Standard Serial Number (ISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.04885

Language

  • eng