Improvement of C3A cell metabolism for usage in bioartificial liver support systems.
OBJECTIVE
The use of cell lines in bioartificial liver support systems (BALSS) to treat fulminant hepatic failure (FHF) is hindered by their reduced metabolic functions, which could be further decreased by the patient's serum/plasma. Hence, the aim of this study was to (i) test the effect of the FHF serum on C3A cell metabolism; (ii) precondition the cells to improve their metabolic capacity.


METHODS
C3A cells were preconditioned in a medium developed at the University of Edinburgh (UoE) or a 10% FHF serum medium. Metabolism capacity was assessed on days 3, 7 and 10 and compared with primary porcine hepatocytes. Preconditioned-cell metabolism was reassessed after (i) passage and (ii) incubation with 10% FHF serum.


RESULTS
UoE-preconditioned cells showed time-dependent increase in gluconeogenesis (500%), ureogenesis (200%), galactose elimination (240%) albumin synthesis (250%). These results were in the same order of magnitude as the ones obtained with primary porcine hepatocytes and were further enhanced by cell passage. UoE-preconditioning prevented the decrease of metabolism induced by acute incubation with FHF serum on control C3A cells. Preconditioning with FHF serum did not improve cell metabolism.


CONCLUSIONS
Cell preconditioning with UoE-medium increases metabolic capacity and would greatly improve BALSS efficacy.
Department of Hepatology, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB Scotland, UK. celine.filippi@ed.ac.uk
Céline
C
Filippi
Steven A
SA
Keatch
Deepa
D
Rangar
Leonard J
LJ
Nelson
Peter C
PC
Hayes
John N
JN
Plevris
D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D005690:Galactose / Q000378:metabolism; D005943:Gluconeogenesis; D018197:Hepatoblastoma / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D017114:Liver Failure, Acute / Q000097:blood*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D019164:Liver, Artificial; D013552:Swine; D013997:Time Factors; D014508:Urea / Q000378:metabolism
D000418:Albumins; D003470:Culture Media; D014508:Urea; D005690:Galactose