THE RELATION BETWEEN HEPATOCELLULAR DAMAGE AND ACTIVATION OF FAT-STORING CELL-PROLIFERATION IN-VITRO

This study is devoted to the role which damaged hepatocytes might play in the mechanism of fat-storing cell activation. With increasing cult ure time conditioned medium from hormone- and serum-free suspension cu ltures of hepatocytes stimulates significantly the proliferation of fa t-storing cells (FSC) maintained in non-confluent monolayers under red uced fetal calf serum (0.5%). The increase of the growth promoting act ivity was paralleled by the elevation of LDH and AST activities in the se media and by the decrease of cell viability checked by Trypan blue uptake. Essentially similar results were obtained from monolayers of h epatocytes cultured in the absence or presence of various cytotoxic ag ents. The growth promoting activity for FSC increased with culture tim e of hepatocytes during which LDH, AST activity and total protein conc entration in the medium became also elevated. Under all conditions the growth promoting activity of hepatocyte media for FSC was correlated highly positively and significantly with LDH (r = 0.90), AST (r = 0.94 ), and total protein (r = 0.82). These results point to a newly recogn ized mechanism of FSC activation in which damaged parenchymal liver ce lls play a significant role at the onset of liver fibrogenesis.