S. Beken et al., Effect of extracellular matrix composition on the expression of glutathione S-transferase isoenzymes in organotypical hepatocyte cultures, TOX VITRO, 13(4-5), 1999, pp. 571-577
Collagen gel sandwich and immobilization cultures of hepatocytes, using hyd
rated collagen type I as extracellular matrix (ECM), have been proposed as
long-term in vitro models in pharmacotoxicology. The in vivo ECM compositio
n in the space of Disse is. however, much more complex. As a differentiated
hepatocyte phenotype is thought to be highly dependent on ECM composition
and biophysical characteristics, we modulated the ECM to mimic the bt vivo
situation. Moreover, commercially available collagen type I (Boehringer-Ing
elheim) was compared to the one prepared in the laboratory from rat tails.
ECM composition had no effect on albumin secretion or hepatocyte morphology
in both collagen gel sandwich and immobilization cultures. Total, Alpha an
d Mu class GST activities in organotypical cultures with a complex or a sim
ple collagen type I ECM were similar. The Pi class GST activity increased a
s a function of culture time in all culture models. Thus, mimicking the in
vivo composition of the ECM did not improve the changes in GST expression t
hat were observed in simple collagen gel cultures. The collagen type I matr
ix is therefore assumed to confer sufficient protection to help the hepatoc
ytes to maintain their differentiated phenotype to a certain extent. Moreov
er, we hypothesize that the collagen gel matrix may act as a scaffold to ke
ep newly synthesized ECM components in the proximity of the basolateral sur
faces of the hepatocytes. (C) 1999 Elsevier Science Ltd. All rights reserve
d.