The newly established human hepatocyte cell line: application for the bioartificial liver.
OBJECTIVE
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.
Harimoto
Norifumi
N
The Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. harimoto@surg2.med.kyushu-u.ac.jp
Taketomi
Akinobu
A
Kitagawa
Dai
D
Kuroda
Yousuke
Y
Itoh
Shinji
S
Gion
Tomonobu
T
Tanaka
Shinji
S
Shirabe
Ken
K
Shimada
Mitsuo
M
Maehara
Yoshihiko
Y
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006498:Hepatectomy; D018197:Hepatoblastoma; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology / Q000637:transplantation*; D006801:Humans; D017114:Liver Failure, Acute / Q000401:mortality / Q000628:therapy*; D008113:Liver Neoplasms; D019164:Liver, Artificial; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000235:genetics; D013154:Spleen; D015996:Survival Rate; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection
D013937:Thymidine Kinase