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3-D in vitro model of early skeletal muscle development

Cheema, U; Yang, SY; Mudera, V; Goldspink, GG; Brown, RA; (2003) 3-D in vitro model of early skeletal muscle development. CELL MOTIL CYTOSKEL , 54 (3) 226 - 236. 10.1002/cm.10095.

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Abstract

An understanding of the mechanical and mechano-molecular responses that occur during the differentiation of mouse c2c12 myoblasts in 3-D culture is critical for understanding growth, which is important for progress towards producing a tissue-engineered muscle construct. We have established the main differences in force generation between skeletal myoblasts, dermal fibroblasts, and smooth muscle cells in a 3-D culture model in which cells contract a collagen gel construct. This model was developed to provide a reproducible 3-D muscle organoid in which differences in force generation could be measured, as the skeletal myoblasts fused to form myotubes within a collagen gel. Maintenance of the 3-D culture under sustained uni-axial tension, was found to promote fusion of myoblasts to form aligned multi-nucleate myotubes. Gene expression of both Insulin Like Growth Factor (IGF-1 Ea) and an isoform of IGF-1 Ea, Mechano-growth factor (IGF-1 Eb, also termed MGF), was monitored in this differentiating collagen construct over the time course of fusion and maturation (0-7 days). This identified a transient surge in both IGF-1 Ea and MGF expression on day 3 of the developing construct. This peak of IGF-1 Ea and MGF expression, just prior to differentiation, was consistent with the idea that IGF-1 Ea stimulates differentiation through a Myogenin pathway [Florini et al., 1991: Mol. Endocrinol. 5:718-724]. MGF gene expression was increased 77-fold on day 3, compared to a 36-fold increase with IGF-1 Ea on day 3. This indicates an important role for MGF in either differentiation or, more likely, a response to mechanical or tensional cues. Cell Motil. Cytoskeleton 54:226-236, 2003. (C) 2003 Wiley-Liss, Inc.

Type: Article
Title: 3-D in vitro model of early skeletal muscle development
DOI: 10.1002/cm.10095
Keywords: cell mechanics, mechano-growth factor (MGF), myoblast differentiation, myotubes, 3-D muscle organoid, IGF-1 Ea, MECHANICAL CELL STIMULATOR, COLLAGEN LATTICES, SATELLITE CELLS, FIBROBLAST CONTRACTION, IGF-I, GROWTH, FORCES, EXPRESSION, DIFFERENTIATION, 2ND-MESSENGERS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Ortho and MSK Science
URI: http://discovery.ucl.ac.uk/id/eprint/139911
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