In vitro migration of rat stellate cells during activation

Histopathological studies have demonstrated that stellate cells accumulate in the post-necrotic area remote from sinusoidal walls. This fact indicates that stellate cells may undergo migration in addition to local proliferati on. The present in vitro study was designed to visualize their migration an d clarify its molecular regulation. For this purpose, Cell Culture Insert w ith 8 mu m-pores was used for the assay instead of a classical Boyden chamb er. Stellate cells were observed to migrate from the inner side of the memb rane to its outer side, which was monitored under microscope after staining the cells for Giemsa. Nearly zero and 18% of freshly isolated stellate cel ls underwent migration at 24 h and 48 h, respectively, after culture in ser um-containing medium without any other stimuli. Migrated stellate cells exh ibited elongated and stretched structure while resting cells had small and rounded shapes. However, the cells on both side of membrane contained subst antial amount of lipid droplets and exhibited immunoreactive desmin, but no t smooth muscle alpha-actin. Addition of platelet-derived growth factor or Kupffer cells into the lower chamber significantly promoted the migration. In contrast, dexamethasone and interferon-gamma attenuated the migration. O n the other hand, myofibroblastic cells, which were transformed from stella te cells after culturing for 14 days, exhibited prominent migration even in the absence of stimuli. These data indicate that stellate cells acquire th eir migratory potency during activation.