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

众所周知，许多因素参与肝脏的再生和组织修复。细胞外基质尤其是肝Disse间隙网硬蛋白纤维的参与以及肝细胞与肝窦内皮细胞之间的相互作用被认为是其中的重要因素。在先前科学研究补助金（C）5857032的支持下，我们发现网硬蛋白纤维由胶原蛋白、糖蛋白和蛋白聚糖组成，并开发为利用每种组分作为成年大鼠肝细胞原代培养物的培养基质。在本研究资助项目（C）的支持下，我们发现：（1）成年大鼠肝细胞对各种成分的特异性组装，（2）肝细胞对蛋白多糖作为底物的固态反应形成多细胞球状体; 3）多细胞球体内的肝细胞具有形态学上确定的分化结构和生化上确定的分化功能，4）多细胞球体不仅由肝细胞形成，而且由异型细胞、肝细胞和窦内皮细胞混合形成; 5）由于大量的胆管样结构和Golji复合物仅在异型细胞-球状体中观察到，异型细胞-球状体的组织结构水平高于肝细胞-球状体; 6）新鲜大鼠血清含有高分子量糖蛋白，其诱导大鼠肝窦内皮细胞增殖。

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.