Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs

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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.

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Lauran Madden

Department of Biomedical Engineering, Duke University, Durham, United States

Competing interests
The authors declare that no competing interests exist.
Mark Juhas

Department of Biomedical Engineering, Duke University, Durham, United States

Competing interests
The authors declare that no competing interests exist.
William E Kraus

Department of Medicine, Duke University School of Medicine, Durham, United States

Competing interests
The authors declare that no competing interests exist.
George A Truskey

Department of Biomedical Engineering, Duke University, Durham, United States

Competing interests
The authors declare that no competing interests exist.
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).

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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.