TY - JOUR
T1 - The newly established human hepatocyte cell line
T2 - Application for the bioartificial liver
AU - Harimoto, Norifumi
AU - Taketomi, Akinobu
AU - Kitagawa, Dai
AU - Kuroda, Yousuke
AU - Itoh, Shinji
AU - Gion, Tomonobu
AU - Tanaka, Shinji
AU - Shirabe, Ken
AU - Shimada, Mitsuo
AU - Maehara, Yoshihiko
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jhep.2004.11.038
DO - 10.1016/j.jhep.2004.11.038
M3 - Article
C2 - 15763342
AN - SCOPUS:20044389075
SN - 0168-8278
VL - 42
SP - 557
EP - 564
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -