Engineered myovascular tissues for studies of endothelial/satellite cell interactions.

In native skeletal muscle, capillaries reside in close proximity to muscle stem cells (satellite cells, SCs) and regulate SC numbers and quiescence through partially understood mechanisms that are difficult to study in vivo. This challenge could be addressed by the development of a 3-dimensional (3D) in vitro model of vascularized skeletal muscle harboring both a pool of quiescent SCs and a robust network of capillaries. Still, studying interactions between SCs and endothelial cells (ECs) within a tissue-engineered muscle environment has been hampered by the incompatibility of commercially available EC media with skeletal muscle differentiation.

Myoblast deactivation within engineered human skeletal muscle creates a transcriptionally heterogeneous population of quiescent satellite-like cells.

Satellite cells (SCs), the adult Pax7-expressing stem cells of skeletal muscle, are essential for muscle repair. However, in vitro investigations of SC function are challenging due to isolation-induced SC activation, loss of native quiescent state, and differentiation to myoblasts. In the present study, we optimized methods to deactivate in vitro expanded human myoblasts within a 3D culture environment of engineered human skeletal muscle tissues ("myobundles").