Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs.
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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.
human skeletal muscle
Reproducibility of Results
Published Version (Please cite this version)10.7554/eLife.04885
Publication InfoMadden, Lauran; Juhas, Mark; Kraus, William E; Truskey, George A; & Bursac, Nenad (2015). Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs. Elife, 4. pp. e04885. 10.7554/eLife.04885. Retrieved from https://hdl.handle.net/10161/9364.
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Professor of Biomedical Engineering
Bursac's research interests include: Stem cell, tissue engineering, and gene based therapies for heart and muscle regeneration; Cardiac electrophysiology and arrhythmias; Organ-on-chip and tissue engineering technologies for disease modeling and therapeutic screening; Small and large animal models of heart and muscle injury, disease, and regeneration. The focus of my research is on application of pluripotent stem cells, tissue engineering, and gene therapy technologies for: 1) basic s
Richard and Pat Johnson University Distinguished Professor
My training, expertise and research interests range from human integrative physiology and genetics to animal exercise models to cell culture models of skeletal muscle adaptation to mechanical stretch. I am trained clinically as an internist and preventive cardiologist, with particular expertise in preventive cardiology and cardiac rehabilitation. My research training spans molecular biology and cell culture, molecular genetics, and integrative human exercise physiology and metabolism. I pr
R. Eugene and Susie E. Goodson Distinguished Professor of Biomedical Engineering
My research interests focus upon the effect of physical forces on the function of vascular cells and skeletal muscle, cell adhesion, and the design of engineered tissues. Current research projects examine the effect of endothelial cell senescence upon permeability to macromolecules and the response to fluid shear stress, the development of microphysiological blood vessels and muscles for evaluation of drug toxicity and the design of engineered endothelialized blood vessels and skelet
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