COMPARISON OF PORCINE HEPATOCYTES WITH HUMAN HEPATOMA (C3A) CELLS FORUSE IN A BIOARTIFICIAL LIVER SUPPORT SYSTEM

Cells from primary porcine hepatocytes (PPH) and the immortalized huma n hepatoma cell line C3A are both used in bioartificial liver support systems (BALSS), In this work the viability and metabolic capacity of PPH and C3A cells cultured in different media were compared. Also, bec ause the cells come into direct or indirect contact with human blood c omponents in BALSS, the effects of human complement on survival and fu nctions of the cells was evaluated. For short-term culture, maintenanc e of PPH viability was essential for retention of P450IA1 activity (r = 0.882, p < 0.01) and effective ammonia clearance (r = -0.791, p < 0. 01), When cell viability was below 60% P450IA1 activity could not be r ecorded and nitrogen elimination activity significantly diminished. In contrast to PPH, ammonia levels were markedly increased for C3A cells in all culture media tested (p < 0.01). Ammonia increase correlated w ith C3A viability (r = 0.896, p < 0.05), PPH metabolic function was su perior to that of the C3A cell line when evaluated by P450IA1 activity , ammonia removal, and amino acid metabolism. When PPH were incubated in human plasma (HP) or human serum (HS) there was rapid and irreversi ble deterioration of viability occurring within 9 h. This toxic effect could be prevented by the inactivation of complement, When sodium cit rate dissolved in dextrose was added to medium, there was considerable damage to both PPH and the C3A cell line, However, there was no demon strable toxic effect when hepatic cells of either type were exposed to heparin, We conclude that PPH cultivated in complement-inactivated HP or HS are to be preferred to C3A for clinical application of BALSS, a nd that heparin should be preferred for anticoagulation in BALSS, (C) 1998 Elsevier Science Inc.