RRC ID 42408
著者 Wang N, Tsuruoka S, Yamamoto H, Enosawa S, Omasa T, Sata N, Matsumura T, Nagai H, Fujimura A.
タイトル The bioreactor with CYP3A4- and glutamine synthetase-introduced HepG2 cells: treatment of hepatic failure dog with diazepam overdosage.
ジャーナル Artif Organs
Abstract A novel recombinant human hepatic cell line, CYP3A4- and glutamine synthetase (GS, an enzyme which converts ammonium ion and glutamate to glutamine)-introduced HepG2 (HepG2-GS-CYP3A4), was established. Its usefulness in a large-scale culture with a circulatory bioreactor in vitro and in dog models of ischemic hepatic failure with acute diazepam (DZP, a substrate of CYP3A4) overdosage was further examined. HepG2-GS-CYP3A4 expressed about 9 times larger amounts of CYP3A4 protein than a control. After incubation with HepG2-GS-3A4 cells in a circulatory bioreactor for 24 h, ammonia and DZP concentrations in the culture medium significantly decreased by about 40%. Furthermore, this system improved the survival time and decreased serum concentrations of DZP, ammonia, and transaminase in dogs with ischemic hepatic failure plus acute DZP overdosage. The mean survival time with bioreactor with HepG2-GS-3A4 was 42.7 +/- 3.6 h, which was significantly longer than that without reactor, with reactor (no cells), and with HepG2-GS (23.4 +/- 2.8, 22.1 +/- 2.4, and 31 +/- 3.7 h, respectively). Therefore, it is concluded that this bioartificial liver could be a good tool for the treatment of dogs with hepatic failure and that it could potentially be a bridging procedure to liver transplantation.
巻・号 29(8)
ページ 681-4
公開日 2005-8-1
DOI 10.1111/j.1525-1594.2005.29107.x
PII AOR29107
PMID 16048486
MeSH Animals Bioreactors* Cell Line Cricetinae Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System / metabolism* Diazepam / administration & dosage Diazepam / adverse effects Diazepam / analysis Dogs Drug Overdose Glutamate-Ammonia Ligase / metabolism* Humans Hypnotics and Sedatives / administration & dosage Hypnotics and Sedatives / adverse effects Hypnotics and Sedatives / analysis Liver Failure / metabolism Liver Failure / therapy* Liver Failure / veterinary Liver, Artificial*
IF 2.259
引用数 17
WOS 分野 TRANSPLANTATION ENGINEERING, BIOMEDICAL
リソース情報
ヒト・動物細胞 Hep G2