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

TitleBioengineered human myobundles mimic clinical responses of skeletal muscle to drugs.
Publication TypeJournal Article
Year of Publication2015
AuthorsMadden, L, Juhas, M, Kraus, WE, Truskey, GA, and Bursac, N
JournaleLife
Volume4
Start Pagee04885
Paginatione04885
Date Published01/2015
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.

DOI10.7554/elife.04885
Short TitleeLife