title: TGF-β1 enhances contractility in engineered skeletal muscle.
abstract: Scaffoldless engineered 3D skeletal muscle tissue created from satellite cells offers the potential to replace muscle tissue that is lost due to severe trauma or disease. Transforming growth factor-beta 1 (TGF-β1) plays a vital role in mediating migration and differentiation of satellite cells during the early stages of muscle development. Additionally, TGF-β1 promotes collagen type I synthesis in the extracellular matrix (ECM) of skeletal muscle, which provides a passive elastic substrate to support myofibres and facilitate the transmission of force. To determine the role of TGF-β1 in skeletal muscle construct formation and contractile function in vitro, we created tissue-engineered 3D skeletal muscle constructs with varying levels of recombinant TGF-β1 added to the cell culture medium. Prior to the addition of TGF-β1, the primary cell population was composed of 75% Pax7-positive cells. The peak force for twitch, tetanus and spontaneous force were significantly increased in the presence of 2.0 ng/ml TGF-β1 when compared to 0, 0.5 and 1.0 ng/ml TGF-β1. Visualization of the cellular structure with H&E and with immunofluorescence staining for sarcomeric myosin heavy chains and collagen type I showed denser regions of better organized myofibres in the presence of 2.0 ng/ml TGF-β1 versus 0, 0.5 and 1.0 ng/ml. The addition of 2.0 ng/ml TGF-β1 to the culture medium of engineered 3D skeletal muscle constructs enhanced contractility and extracellular matrix organization.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-2200, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Weist
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wellington
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Bermudez
authors.forename: Tatiana Y
authors.initials: TY
authors.lastname: Kostrominova
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Mendias
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Arruda
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Larkin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D009124:Muscle Proteins / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism; D023822:Tissue Engineering; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D009124:Muscle Proteins; D053773:Transforming Growth Factor beta1