Primary hepatocytes outperform Hep G2 cells as the source of biotransformation functions in a bioartificial liver.
OBJECTIVE
Metabolic activity of transformed human liver (Hep G2) cells and primary rat hepatocytes were compared during in vitro application of a gel entrapment bioartificial liver.


BACKGROUND
Clinical trials of bioartificial liver devices containing either transformed liver cells or primary hepatocytes have been initiated. A study comparing transformed liver cells and primary hepatocytes in a bioartificial liver under similar conditions has not been reported previously.


METHODS
Gel entrapment bioartificial liver devices were inoculated with 100 million cells, Hep G2 cell line (n = 4), or rat hepatocytes (n = 16), and studied for up to 60 days of in vitro cultivation.


RESULTS
Hep G2 cells grew to confluence within the gel entrapment configuration with a doubling time of 20 +/- 3 hours. Rat hepatocytes significantly outperformed Hep G2 cells at confluence in all categories of biotransformation, including ureagenesis (3.5 +/- 0.7 vs. 0.3 +/- 0.1 mumol/hr, p < 0.05), glucuronidation (630 +/- 75 vs. 21 +/- 2 nmol/hr, p < 0.005), sulfation (59 +/- 13 vs. 5 +/- 2 nmol/hr, p < 0.05), and oxidation (233 +/- 38 vs. < 1 nmol/hr, p < 0.005). At the conclusion of one experiment, Hep G2 cells were found in the extracapillary compartment of the bioartificial liver, analogous to the patient's compartment during clinical application.


CONCLUSIONS
Primary rat hepatocytes were superior to the Hep G2 cell line as the source of hepatic function in a bioartificial liver and avoided the potential risk of tumor transmigration from the bioartificial liver into the patient's circulation.
Department of Surgery, University of Minnesota, Minneapolis.
S L
SL
Nyberg
R P
RP
Remmel
H J
HJ
Mann
M V
MV
Peshwa
W S
WS
Hu
F B
FB
Cerra
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001187:Artificial Organs; D001711:Biotransformation; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008012:Lidocaine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014508:Urea / Q000378:metabolism
D000418:Albumins; D007773:Lactates; D019344:Lactic Acid; C075860:3-hydroxylidocaine; D014508:Urea; D008012:Lidocaine; C001173:monoethylglycinexylidide; D005947:Glucose