Primary or established liver cells for a hybrid liver? Comparison of metabolic features.
It is currently in discussion whether or not established liver cell lines can be used for an extracorporeal liver assist device. Thus, metabolic features of primary hepatocytes, immortalized hepatocytes, and hepatoma cells were compared. The ability of these cells to process toxic blood of patients with hepatic failure was investigated by testing their viability in toxin enriched medium that was obtained by toxin separation from patients' blood via a molecular adsorbents recirculating system (MARS). In addition, glucose metabolism, urea synthesis, P450 dependent verapamil metabolism using high performance liquid chromatography, and interleukin-6 induced "acute phase" reaction by sulfodesoxysalicylic acid-polyacrylamide gel electrophoresis detected changes of albumin synthesis were determined in primary hepatocytes and in established liver cells. The viability of hepatoma cells after contact with the toxic compounds coming from the patients' blood was significantly decreased in comparison to that of immortalized hepatocytes and primary hepatocytes. Immortalized hepatocytes and hepatoma cells showed a significantly higher consumption of glucose associated with a significantly higher lactate synthesis. A basic urea synthesis rate could be measured in immortalized hepatocytes and hepatoma cells, but it was significantly lower than that of primary cells. P450 with its subenzyme CYP2C was inducible only in primary hepatocytes and in immortalized cells, but in the latter the enzymatic activity was lower than that of primary cells. The incubation with acute phase mediators resulted in a decrease of albumin synthesis in primary hepatocytes and in hepatoma cells, but it increased the albumin synthesis in immortalized hepatocytes. Summarizing these data, partially beneficial effects can be assumed if established cells are used in an extracorporeal liver assist device. These might include synthesis of some compounds and basic metabolic activities, such as urea synthesis. However, established liver cells showed clearly altered metabolic characteristics. The sufficient removal of toxic compounds requires additional strategies for detoxification by primary hepatocytes in sufficient amounts.
Stange
J
J
Department of Internal Medicine, University of Rostock, Germany.
Mitzner
S
S
Strauss
M
M
Fischer
U
U
Lindemann
S
S
Peters
E
E
Holtz
M
M
Drewelow
B
B
Schmidt
R
R
D000210:Acute-Phase Reaction; D000818:Animals; D001187:Artificial Organs; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005069:Evaluation Studies as Topic; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000166:cytology / Q000378:metabolism; D017114:Liver Failure, Acute / Q000628:therapy; D051379:Mice; D051381:Rats; D014508:Urea / Q000378:metabolism
D007773:Lactates; D019344:Lactic Acid; D014508:Urea; D003577:Cytochrome P-450 Enzyme System; D005947:Glucose