Abstract:
BACKGROUND/AIMS:Bio-artificial liver support systems for treatment of hepatic failure require maintained expression of hepatocyte function in vitro. We studied cultures of human hepatocyte cell-lines proliferating within alginate beads, investigating the hypothesis that 3-dimensional cohesive colonies of hepatocyte cell-lines would achieve polarity and cell-to-cell contact resulting in upregulation of function. METHODS:HepG2 and HHY41 human cell lines in alginate beads were cultured for >20 days. RESULTS:Proliferation was maintained for 20 days. Production of albumin, prothrombin, fibrinogen, alpha-1-acid glycoprotein and alpha-1-antitrypsin was maintained throughout, maximal at days 8-10, when upregulation was 300-1100% compared with monolayer cultures at similar cell number per unit volume. Detoxificatory functions: ethoxyresorufin deethylase activity, androstenedione metabolism, and urea synthesis from arginine was also increased several-fold. Function returned to pre-freezing levels within 18 h of thawing after cryopreservation of cells in alginate. Electron microscopy revealed spherical colonies of cells of cuboidal shape, with cell-to-cell contact via desmosomes and junctional complexes, abundant microvilli, and cytoplasmic appearances suggesting transcriptionally active hepatocytes. CONCLUSION:Hepatocyte cell-lines, proliferating in alginate express a range of liver-specific functions at levels approaching those found in vivo, relevant to their use in liver support systems.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Khalil M,Shariat-Panahi A,Tootle R,Ryder T,McCloskey P,Roberts E,Hodgson H,Selden Cdoi
10.1016/s0168-8278(00)00080-5subject
Has Abstractpub_date
2001-01-01 00:00:00pages
68-77issue
1eissn
0168-8278issn
1600-0641pii
S0168827800000805journal_volume
34pub_type
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pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章
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更新日期:2007-11-01 00:00:00
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