EXPRESSION OF ORGAN-SPECIFIC STRUCTURES AND FUNCTIONS IN LONG-TERM CULTURES OF AGGREGATES FROM ADULT-RAT LIVER-CELLS

Freshly isolated hepatocytes, endothelial cells, Kupffer and fat-stori ng cells from adult rats were found to be able to form spheroidal aggr egates within 24 hr when cultured under serum-free and rotatory condit ions. The ultrastructure, including intracellular organization and ext racellular matrix deposition was investigated in 7-day aggregates by s canning and electron microscopy. The different cell types expressed a histotypic organization and reconstructed their extracellular matrix ( fibronectin and laminin) as well as junctional complexes (desmosomes, tight junctions and gap junctions). The aggregates preserved, over a p eriod of at least 7 days, high albumin expression (mRNA) and secretion as well as high secretion of the acute phase protein T-kininogen. Dex amethasone (10(-7) M) increased the tyrosine aminotransferase activity fourfold after a 24-hr exposure. Aggregates cultured in the presence of 10(-7) hr dexamethasone showed an increased expression and secretio n of albumin concomitantly with a decrease in T-kininogen secretion. I nduction of 7-ethoxycoumarin O-deethylase (ECOD) was effective after e xposure to 3-methylcholanthrene or Aroclor for 48 hr. Up to a 13-fold increase in (ECOD) activity was found. The results demonstrate that sp heroidal cultures of liver cell aggregates obtained under rotatory con ditions provide a useful model for studies on the combined cellular in teractions between non-parenchymal liver cells and hepatocytes from ad ult rats (C) 1997 Elsevier Science Ltd.