Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs

  1. Lauran Madden
  2. Mark Juhas
  3. William E Kraus
  4. George A Truskey
  5. Nenad Bursac  Is a corresponding author
  1. Duke University, United States
  2. Duke University School of Medicine, United States

Abstract

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.

Article and author information

Author details

  1. Lauran Madden

    Department of Biomedical Engineering, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Mark Juhas

    Department of Biomedical Engineering, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. William E Kraus

    Department of Medicine, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. George A Truskey

    Department of Biomedical Engineering, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Nenad Bursac

    Department of Biomedical Engineering, Duke University, Durham, United States
    For correspondence
    nbursac@duke.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Human subjects: Human skeletal muscle samples were obtained through standard needle biopsy or surgical waste under Duke University IRB approved protocols (Pro00048509 and Pro00012628).

Reviewing Editor

  1. Amy J Wagers, Harvard University, United States

Publication history

  1. Received: September 23, 2014
  2. Accepted: January 8, 2015
  3. Accepted Manuscript published: January 9, 2015 (version 1)
  4. Version of Record published: February 16, 2015 (version 2)

Copyright

© 2015, Madden et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Lauran Madden
  2. Mark Juhas
  3. William E Kraus
  4. George A Truskey
  5. Nenad Bursac
(2015)
Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs
eLife 4:e04885.
https://doi.org/10.7554/eLife.04885
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