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-storing cells from adult rats were found to be able to form spheroidal aggregates within 24 hr when cultured under serum-free and rotatory conditions. The ultrastructure, including intracellular organization and extracellular matrix deposition was investigated in 7-day aggregates by scanning 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 period of at least 7 days, high albumin expression (mRNA) and secretion as well as high secretion of the acute phase protein T-kininogen. Dexamethasone (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 secretion of albumin concomitantly with a decrease in T-kininogen secretion. Induction of 7-ethoxycoumarin O-deethylase (ECOD) was effective after exposure to 3-methylcholanthrene or Aroclor for 48 hr. Up to a 13-fold increase in (ECOD) activity was found. The results demonstrate that spheroidal cultures of liver cell aggregates obtained under rotatory conditions provide a useful model for studies on the combined cellular interactions between non-parenchymal liver cells and hepatocytes from adult rats (C) 1997 Elsevier Science Ltd.