RT Journal Article
SR Electronic
T1 GENE EXPRESSION IN HUMAN HEPATOCYTES IN SUSPENSION AFTER ISOLATION IS SIMILAR TO THE LIVER OF ORIGIN, IS NOT AFFECTED BY HEPATOCYTE COLD STORAGE AND CRYOPRESERVATION, BUT IS STRONGLY CHANGED AFTER HEPATOCYTE PLATING
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 870
OP 879
DO 10.1124/dmd.105.007708
VO 34
IS 5
A1 Lysiane Richert
A1 Michael J. Liguori
A1 Catherine Abadie
A1 Bruno Heyd
A1 Georges Mantion
A1 Nermin Halkic
A1 Jeffrey F. Waring
YR 2006
UL http://dmd.aspetjournals.org/content/34/5/870.abstract
AB Isolated primary human hepatocytes are a well accepted system for evaluating pharmacological and toxicological effects in humans. However, questions remain regarding how culturing affects the liver-specific functions of the hepatocytes. In addition, cryopreservation could also potentially affect the differentiation state of the hepatocytes. The first aim of the present study was to compare gene expression in freshly isolated primary hepatocytes to that of the liver of origin and to evaluate the expression changes occurring after cryopreservation/thawing, both when maintained in suspension and after plating. The second aim of the present study was to evaluate gene expression in hepatocytes after cold storage of suspensions up to 24 h compared with freshly isolated hepatocytes in suspension. Our results show that the gene expression in freshly isolated human hepatocytes in suspension after isolation is similar to that of the liver of origin. Furthermore, gene expression in primary human hepatocytes in suspension is not affected by hepatocyte cold storage and cryopreservation. However, the gene expression is profoundly affected in monolayer cultures after plating. Specifically, gene expression changes were observed in cultured relative to suspensions of human hepatocytes that are involved in cellular processes such as phase I/II metabolism, basolateral and canalicular transport systems, fatty acid and lipid metabolism, apoptosis, and proteasomal protein recycling. An oxidative stress response may be partially involved in these changes in gene expression. Taken together, these results may aid in the interpretation of data collected from human hepatocyte experiments and suggest additional utility for cold storage and cryopreservation of hepatocytes. The American Society for Pharmacology and Experimental Therapeutics