UC Davis

Muscle regeneration depends on satellite cells which, prior to injury, are quiescent and located on the periphery of myofibers. When an injury occurs, satellite cells are activated and migrate to the injury to fuse with damaged myofibers and rebuild the tissue. In certain muscle diseases, such as Duchenne muscular dystrophy (DMD), satellite cells do not function properly and do not effectively regenerate tissue. DMD is characterized by chronic fibrosis, where an excess of collagen builds up and replaces functional tissue. We propose that satellite cells undergo damage when migrating through small spaces in the dense fibrotic tissue. In this thesis, we demonstrate that human myoblasts, active cells already committed to a myogenic lineage, undergo high levels of nuclear rupture and incur DNA damage when migrating through small-diameter pores. They also exhibit impaired adhesion and differentiation, indicating that constricted migration can impair the regenerative capacity of cells.Tissue engineering can be used to improve studies of muscle cells. We present a platform to grow muscle microtissues from human myoblasts using an extracellular matrix (ECM) protein-based hydrogel for structural and signaling support. This platform has the potential to expand and improve in vitro studies of muscle, including studies aimed at understanding the interactions between the muscle ECM and muscle resident cells. It can be customized to model fibrotic diseases using collagen, and it can be used as an additional measure of myoblast function following constricted migration with increased physiological relevance