Chemotactic factors enhance myogenic cell migration across an endothelial monolayer

Recent reports revealed that myogenic progenitors, derived from either bone marrow or muscle can migrate into muscle tissue and participate in myofibe r regeneration, when injected in the peripheral circulation. This observati on might open a new strategy for the treatment of muscular dystrophies. The signals involved in myoblast recruitment from circulation are at present p oorly understood. To investigate myoblast migration we used a transwell ass ay in which murine myoblasts and myogenic cell lines were seeded on micropo rous membrane covered by an endothelial monolayer and chemotactic factors w ere added in the lower chamber. We demonstrated that myoblasts are able to cross the endothelium and that this process can be modulated. In particular among tested factors, we observed a gradient of chemotactic activity as fo llows: HGF much greater than RANTES > PDGF-A > PDGF-B > FGF much greater th an TNF-alpha > IFN-gamma > EGF. Endothelial and myoblast expression of Pax3 (a transcription factor expressed by embryonic migrating myogenic cells) a nd cytokine transcripts (TNF-alpha, IFN-gamma) was also monitored either at the basal level and after transmigration. We observed increased Pax3 expre ssion after interaction of C2C12 myoblasts with endothelial cells. We consi der that any new report elucidating the molecular signals involved in myobl ast migration may be useful toward the development of systemic cellular-med iated gene therapy of muscle diseases. (C) 2001 Academic Press.