3D skeletal muscle model recapitulating the myostatin knockout phenotypic and mitochondrial metabolic features

3D cell culture, using a variety of bioengineering techniques, enables muscle cells to be cultured in more structural and functional biomimetic conditions than 2D cell culture. Here, we tested the ability of an engineered 3D skeletal muscle model to recapitulate in vivo metabolic muscle response. First, C2C12 myoblasts in 3D cultures showed improved myogenesis, attested by increased differentiation time, myotube formation, and gene expression of differentiated muscle markers. At the functional level, the 3D muscle culture displayed contractile properties and proper mitochondrial respiration. Second, to highlight the interest of such system we used primary myoblasts derived from myostatin knockout (Mstn^-/-) mice. When compared to control wild-types 3D myotubes, 3D myotubes made from Mstn^-/- myoblasts exhibit a hypertrophic phenotype associated with a decrease mitochondrial oxygen consumption, consistent with the skeletal muscle characteristics of Mstn^-/- mice. Our findings show that 3D primary myotubes retain their in vivo phenotype in culture. This provides a useful framework for studying the underlying mechanisms of a various genetic muscle diseases, as well as for screening therapeutic drugs.