Home LiteratureArticle Details
PMID: 8024360 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Primary hepatocytes outperform Hep G2 cells as the source of biotransformation functions in a bioartificial liver.

Annals of surgery ·Vol. 220 ·No. 1 ·1994-07-00 ·Pages 59-67

Nyberg SL, Remmel RP, Mann HJ, Peshwa MV, Hu WS, Cerra FB

Abstract

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. 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. 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. 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. 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.

MeSH Terms
Albumins/metabolism Animals Artificial Organs Biotransformation Cell Line, Transformed Cell Transformation, Neoplastic/metabolism,pathology Cells, Cultured Glucose/metabolism Lactates/metabolism Lactic Acid Lidocaine/analogs & derivatives,metabolism,pharmacokinetics Liver/cytology,metabolism Male Oxygen Consumption Rats Rats, Sprague-Dawley Time Factors Urea/metabolism
Chemicals
Albumins Lactates Lactic Acid 3-hydroxylidocaine Urea Lidocaine monoethylglycinexylidide Glucose
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Nyberg S L
Department of Surgery, University of Minnesota, Minneapolis.
Remmel R P
Mann H J
Peshwa M V
Hu W S
Cerra F B
References (49)
49 references, click to expand
  1. Bilirubin conjugation by an artificial liver composed of cultured cells and synthetic capillaries.
    Trans Am Soc Artif Intern Organs. 1975;21:16-27 PMID: 238327
  2. Liver assist devices (LADs) will not be used to treat fulminant hepatic failure (FHF), but its consequences, namely hepatic encephalopathy (HE)
    Artif Organs. 1993 Jan;17(1):43-5 PMID: 8422234
  3. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen.
    Science. 1980 Jul 25;209(4455):497-9 PMID: 6248960
  4. Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line.
    Nature. 1979 Dec 6;282(5739):615-6 PMID: 233137
  5. Human hepatoma cells secrete single chain factor X, prothrombin, and antithrombin III.
    Blood. 1984 Jul;64(1):194-204 PMID: 6329378
  6. Induction of drug metabolizing enzymes in human liver cell line Hep G2.
    FEBS Lett. 1985 Apr 22;183(2):219-22 PMID: 3921402
  7. HepG2. A human hepatoblastoma cell line exhibiting defects in bile acid synthesis and conjugation.
    J Biol Chem. 1986 Feb 15;261(5):2197-201 PMID: 3003100
  8. Drug metabolism by the human hepatoma cell, Hep G2.
    Biochem Biophys Res Commun. 1987 Feb 27;143(1):52-7 PMID: 3030322
  9. Growth and hepatospecific gene expression of human hepatoma cells in a defined medium.
    In Vitro Cell Dev Biol. 1987 May;23(5):349-54 PMID: 3034851
  10. Overcoming retention time shifts as a source of error in HPLC analysis.
    J Chromatogr Sci. 1987 Apr;25(4):158-63 PMID: 3584387
  11. Induction and activity of several isoenzymes of cytochrome P-450 in primary cultures of rat hepatocytes, in comparison with in vivo data.
    Mol Toxicol. 1987-1988 Fall;1(4):373-81 PMID: 3509691
  12. UDP-glucuronosyltransferases.
    Pharmacol Ther. 1989;43(2):261-89 PMID: 2506584
  13. Lidocaine metabolism in human liver microsomes by cytochrome P450IIIA4.
    Clin Pharmacol Ther. 1989 Nov;46(5):521-7 PMID: 2582709
  14. Metabolism of lidocaine by purified rat liver microsomal cytochrome P-450 isozymes.
    Biochem Pharmacol. 1989 Dec 15;38(24):4439-44 PMID: 2604746
  15. Hep G2 cells as a resource for metabolic studies: lipoprotein, cholesterol, and bile acids.
    FASEB J. 1990 Feb 1;4(2):161-8 PMID: 2153592
  16. Use of hepatocytes in adhesion and suspension cultures for liver support bioreactors.
    Int J Artif Organs. 1989 Dec;12(12):788-92 PMID: 2613360
  17. Characterization of a transforming N-ras gene in the human hepatoma cell line Hep G2: additional evidence for the importance of c-myc and ras cooperation in hepatocarcinogenesis.
    Cancer Res. 1990 Mar 1;50(5):1521-7 PMID: 2154325
  18. Variation in drug-metabolizing enzyme activities during the growth of human Hep G2 hepatoma cells.
    Xenobiotica. 1990 Apr;20(4):435-41 PMID: 2161167
  19. HepG2 cells: an in vitro model for P450-dependent metabolism of acetaminophen.
    Biochem Biophys Res Commun. 1993 Jan 15;190(1):15-9 PMID: 8380689
  20. Cyclosporin A metabolism in human liver, kidney, and intestine slices. Comparison to rat and dog slices and human cell lines.
    Drug Metab Dispos. 1992 Nov-Dec;20(6):802-9 PMID: 1362930
  21. Hepatocyte function in a hollow fiber bioreactor: a potential bioartificial liver.
    J Surg Res. 1992 Dec;53(6):549-57 PMID: 1494286
  22. Use of a novel bioartificial liver in a patient with acute liver insufficiency.
    Surgery. 1993 Mar;113(3):340-3 PMID: 8441969
  23. Culturing of primary hepatocytes as entrapped aggregates in a packed bed bioreactor: a potential bioartificial liver.
    In Vitro Cell Dev Biol. 1993 Mar;29A(3 Pt 1):249-54 PMID: 8463190
  24. Demonstration of biochemical function by extracorporeal xenohepatocytes in an anhepatic animal model.
    Transplant Proc. 1993 Apr;25(2):1944-5 PMID: 8470236
  25. Development of a hybrid bioartificial liver.
    Ann Surg. 1993 May;217(5):502-9; discussion 509-11 PMID: 8489313
  26. p53 gene mutation and integrated hepatitis B viral DNA sequences in human liver cancer cell lines.
    Carcinogenesis. 1993 May;14(5):987-92 PMID: 8389256
  27. Artificial liver: a forthcoming attraction.
    Hepatology. 1993 Jun;17(6):1163-4 PMID: 8514267
  28. Regulation of human liver cytochromes P-450 in family 3A in primary and continuous culture of human hepatocytes.
    Hepatology. 1993 Nov;18(5):1254-62 PMID: 8225233
  29. Assessment of artificial liver support technology.
    Cell Transplant. 1992;1(5):323-41 PMID: 1344305
  30. Extracorporeal application of a gel-entrapment, bioartificial liver: demonstration of drug metabolism and other biochemical functions.
    Cell Transplant. 1993 Nov-Dec;2(6):441-52 PMID: 8167929
  31. Long-term cultures of adult mammalian hepatocytes in hollow fibers as the cellular component of extracorporeal (hybrid) liver assist devices.
    Artif Organs. 1992 Apr;16(2):209-12 PMID: 10078247
  32. Differential induction of human liver UDP-glucuronosyltransferase activities by phenobarbital-type inducers.
    Biochem Pharmacol. 1987 Dec 1;36(23):4137-43 PMID: 2825716
  33. Mixed function oxidase and UDP-glucuronyltransferase activities in the human Hep G2 hepatoma cell line.
    Biochem Pharmacol. 1988 Nov 1;37(21):4111-6 PMID: 2847753
  34. The influence of culture medium composition on drug metabolising enzyme activities of the human liver derived Hep G2 cell line.
    FEBS Lett. 1988 Dec 5;241(1-2):15-8 PMID: 2848717
  35. Modulation of the liver specific phenotype in the human hepatoblastoma line Hep G2.
    In Vitro Cell Dev Biol. 1989 Feb;25(2):217-22 PMID: 2466032
  36. Neoplastic transformation and lineage switching of rat liver epithelial cells by retrovirus-associated oncogenes.
    Mol Carcinog. 1988;1(3):189-95 PMID: 3074814
  37. The pathogenesis and treatment of hepatic encephalopathy: evidence for the involvement of benzodiazepine receptor ligands.
    Pharmacol Rev. 1991 Mar;43(1):27-71 PMID: 1674609
  38. Mammalian hepatocytes as a foundation for treatment in human liver failure.
    J Cell Biochem. 1991 Apr;45(4):359-65 PMID: 1646208
  39. Bioartificial liver using hepatocytes on biosilon microcarriers: treatment of chemically induced acute hepatic failure in rats.
    Artif Organs. 1991 Jun;15(3):189-97 PMID: 1867529
  40. A hybrid artificial liver system. Function of cultured monolayer pig hepatocytes in plasma from hepatic failure patients.
    ASAIO Trans. 1991 Jul-Sep;37(3):M337-8 PMID: 1751175
  41. Interleukin-6 down regulates the expression of transcripts encoding cytochrome P450 IA1, IA2 and IIIA3 in human hepatoma cells.
    Biochem Biophys Res Commun. 1992 Apr 30;184(2):960-5 PMID: 1374245
  42. Reversal of fulminant hepatic failure using an extracorporeal liver assist device.
    Hepatology. 1992 Jul;16(1):60-5 PMID: 1618484
  43. Variant protein patterns in hepatomas and transformed liver cell lines as determined by high resolution two-dimensional gel electrophoresis (2DE).
    Carcinogenesis. 1992 Jul;13(7):1177-83 PMID: 1638684
  44. Selection of variant hepatoma cells in liver-specific growth media: regulation at the mRNA level.
    Differentiation. 1992 May;50(1):25-33 PMID: 1322334
  45. Hepatocyte culture systems for artificial liver support: implications for critical care medicine (bioartificial liver support).
    Crit Care Med. 1992 Aug;20(8):1157-68 PMID: 1643896
  46. Immunoprotection of xenocytes in a hollow fiber bioartificial liver.
    ASAIO J. 1992 Jul-Sep;38(3):M463-7 PMID: 1457903
  47. Does a porcine hepatocyte hybrid artificial liver prolong the survival time of anhepatic rabbits?
    ASAIO J. 1992 Jul-Sep;38(3):M468-72 PMID: 1457904
  48. Improved liver function following treatment with an extracorporeal liver assist device.
    Artif Organs. 1993 Jan;17(1):27-30 PMID: 8422230
  49. Preparation of isolated rat liver cells.
    Methods Cell Biol. 1976;13:29-83 PMID: 177845
Article Info
Journal
Annals of surgery
Abbr.
Ann Surg
ISSN
0003-4932
Published
1994-07-00
Pages
59-67
Language
English
Region
United States
NLM ID
0372354
PMCID
PMC1234288
Subset
IM
Grants
NIDDK NIH HHS · R01-DK45371 · United States
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2