Intrinsic, extrinsic and environmental regulation of muscle satellite cell motility

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Skeletal muscle repair and regeneration requires the activity of satellite cells, a population of myogenic stem cells. Previously, little data existed on the motility of satellite cells a critical component to tissue repair. Using timelapse videomicroscopy to assess satellite cell motility on the surface of single living myofibers, we have identified a requirement for the laminin-binding integrin a7b1 in satellite cell motility, as well as a role for hepatocyte growth factor in promoting directional persistence. We also observed more persistent long-term contact, potential cell-cell attractive and repulsive interaction, and migration between host myofibers. We found that satellite cells express multiple members of each of the four major families of guidance molecules. Satellite cell migration in vivo may be more extensive than currently thought, and could be regulated by combinations of signals including adhesive haptotaxis, soluble factors, and guidance cues. CXCL12/SDF-1 and hepatocyte growth factor/scatter factor (HGF) are included in these released factors satellite cell displacement and velocity and chemotaxis were quantified. Purified HGF and SDF-1a were injected into the Tibialis Anterior muscle (TA) to test the sufficiency of these factors for satellite cell movement in vivo. A better understanding of how satellite cells actually respond to an injury in a healthy muscle and if they are mobilized and motile from a distance will be critical to knowing if they can be induced to move through damaged or diseased muscle tissue.