TGF-[beta]1 enhances contractility in engineered skeletal muscle

• Published in: Journal of tissue engineering and regenerative medicine Vol. 7; no. 7; p. 562
• Main Authors: Weist, Michael R, Wellington, Michael S, Bermudez, Jacob E, Kostrominova, Tatiana Y, Mendias, Christopher L, Arruda, Ellen M, Larkin, Lisa M
• Format: Journal Article
• Language: English
• Published: Hoboken Hindawi Limited 01.07.2013
• Subjects: Regenerative medicine; Tissue engineering
• ISSN: 1932-6254; 1932-7005
• DOI: 10.1002/term.551

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-[beta]1) plays a vital role in mediating migration and differentiation of satellite cells during the early stages of muscle development. Additionally, TGF-[beta]1 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-[beta]1 in skeletal muscle construct formation and contractile function in vitro, we created tissue-engineered 3D skeletal muscle constructs with varying levels of recombinant TGF-[beta]1 added to the cell culture medium. Prior to the addition of TGF-[beta]1, 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 2.0ng/ml TGF-[beta]1 when compared to 0, 0.5 and 1.0ng/ml TGF-[beta]1. 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 2.0ng/ml TGF-[beta]1 versus 0, 0.5 and 1.0ng/ml. The addition of 2.0ng/ml TGF-[beta]1 to the culture medium of engineered 3D skeletal muscle constructs enhanced contractility and extracellular matrix organization. Copyright © 2012 John Wiley & Sons, Ltd. [PUBLICATION ABSTRACT]