Comparison of pig, human and rat hepatocytes as a source of liver specific metabolic functions in culture systems - implications for use in bioartificial liver devices

The limited availability of human hepatocytes results in the use of animal cells in most bioartificial liver support devices. In the present work, clinically relevant liver specific metabolic activities were compared in rat, pig and human hepatocytes cultured on liver-derived biomatrix to optimize the expression of differentiated functions. Pig hepatocytes showed higher rates of diazepam metabolism (2.549+/-0.821 mug/h/million cells vs. 0.474+/-0.079 mug/h/million cells rats, p<0.005, and vs. 0.704+/-0.171 <mu>g/h/million cells in man, p<0.005) and of bilirubin conjugation (21.60116+/-8.433237 <mu>moles/l/24 h vs. 6.786809+/-2.983758 in man, p<0.001 and vs. 9.956538+/-1.781016 <mu>moles/l/24 h in rats, p<0.005). Urea synthesis was similar in pig and in human hepatocytes (150+/-46.3 vs. 144.8+/-21.46 nmoles/h/million cells) and it was lower in rats (84.38+/-35.2; p<0.001 vs. man, p<0.02 vs. pig). High liver specific metabolic activities in cultured pig hepatocytes further support their use as a substitute for human cells in bioartificial liver devices.