RRC ID 42328
著者 Harimoto N, Taketomi A, Kitagawa D, Kuroda Y, Itoh S, Gion T, Tanaka S, Shirabe K, Shimada M, Maehara Y.
タイトル The newly established human hepatocyte cell line: application for the bioartificial liver.
ジャーナル J Hepatol
Abstract BACKGROUND/AIMS:Human hepatocyte cell lines are reported to lose many of their biochemical functions in a hybrid artificial liver support system (HALSS). Differentiation therapy is useful to up-regulate liver function.
METHODS:The human hepatoblastoma cell line HepG2 was transfected with HSV/tk gene. Albumin synthesis and ammonia removal activity were evaluated when HepG2/tk was cultured with histone deacetylase inhibitor (FR228) and peroxisome proliferator activated receptor-gamma ligand (pioglitazone). To investigate the function of HepG2/tk in vivo, cell transplantation for 90% hepatectonized rats was conducted.
RESULTS:We established stable cell lines which expressed HSV/tk and were sensitive to gancyclovir in vitro and in vivo. Both albumin synthesis rate and ammonia removal rate improved for HepG2/tk incubated with FR228 and pioglitazone for 3 days, which induced nuclear transport of p21. Rats with intrasplenic injection of HepG2/tk precultured for 3 days with FR228 and pioglitazone survived significantly longer than the control rats. The ammonia and total bilirubin concentrations were significantly lower in the test group than in the control group. The injection of gancyclovir inhibited the prolonged survival of the rats with precultured HepG2/tk.
CONCLUSIONS:HepG2/tk is safe as well as enhancing high levels of liver function. It will be a potential cell source for HALLS in the future.
巻・号 42(4)
ページ 557-64
公開日 2005-4-1
DOI 10.1016/j.jhep.2004.11.038
PII S0168-8278(05)00006-1
PMID 15763342
MeSH Animals Cell Culture Techniques / methods Cell Differentiation Cell Line, Tumor Disease Models, Animal Hepatectomy Hepatoblastoma Hepatocytes / cytology* Hepatocytes / physiology Hepatocytes / transplantation* Humans Liver Failure, Acute / mortality Liver Failure, Acute / therapy* Liver Neoplasms Liver, Artificial* Rats Rats, Sprague-Dawley Simplexvirus / genetics Spleen Survival Rate Thymidine Kinase / genetics Transfection
IF 20.582
引用数 11
WOS 分野 GASTROENTEROLOGY & HEPATOLOGY
リソース情報
ヒト・動物細胞 Hep G2