title: The newly established human hepatocyte cell line: application for the bioartificial liver.
abstract: 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.
authors.affiliation: 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
authors.forename: Norifumi
authors.initials: N
authors.lastname: Harimoto
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.forename: Dai
authors.initials: D
authors.lastname: Kitagawa
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Shinji
authors.initials: S
authors.lastname: Itoh
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Gion
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: 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
chemical_list: D013937:Thymidine Kinase