A role of extracellular matraix on regeneration of the liver : Involvement of sinusoidal endothelial cell growth factors.

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It was known that many factors are involved in the regeneration and tissue repair of the liver. The involvement of extracellular matrix, especially reticulin fibers in Disse's space of the liver as well as the interaction between hapatocyates and sinusoidal endothelial cells, in these mechanism was considered to be one of important factors. By the support of previous Grant-in-Aid for Scientific Research (C); 5857032, we have found that the reticulin fibers were composed of collagens, glycoproteins and proteoglycans and developed to utilize each component as a culture substrate in the primary culture of adult rat hepatocytes. By the support of the present Grant-in Aid for Scientific Research (C) we found that 1) adult rat hepatocyates assembled to various forms specific to each component; 2) hepatocytes formed multicellular spheroid in responce to the solid state of proteoglycans used as asubstrate; 3) hepatocyates in the multicelluar spheroid exhibited morphologically defined differentiated structures and biochemically defined differentiated functions, and did poor proliferative abiliaty; 4) the multicallular spheroids were not only formed with hepatocytes but also with a mixture of heterotypic cells, hepatocyates and sinusoidal endotahelial cells; 5) since numerous bile canaliculi-like structures and Golji complexes were observed only in the heterotypic cells-spheroids, the level of tissue organization was raised to an upper level in the heterotypic cells-spheroid than the hepatocytes-spheroid; 6) fresh rat serum contained high molecular weight glycoproteins that induced the proliferation of sinusoidal endothelial cells of rat liver.