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The significant improvement of survival times and pathological parameters by bioartificial liver with recombinant HepG2 in porcine liver failure model.

AbstractWe developed a bioartificial liver (BAL) containing human hepatoblastoma cell line, HepG2, with the addition of ammonia removal activity by transfecting a glutamine synthetase (GS) gene and estimated the efficacy using pigs with ischemic liver failure. GS-HepG2 cells showed 15% ammonia removal activity of porcine hepatocytes, while unmodified HepG2 had no such activity. The established GS-HepG2 cells were grown in a circulatory flow bioreactor to 3.5-4.1 x 10(9) cells. Survival time of the animals treated with GS-HepG2 BAL was significantly prolonged compared to the cell-free control (14.52 +/- 5.24 h vs. 8.53 +/- 2.52 h) and the group treated with the BAL consisting of unmodified wild-type HepG2 (9.58 +/- 4.52 h). Comparison showed the cell-containing BAL groups to have significantly fewer incidences of increased brain pressure. Thus, the GS-HepG2 BAL treatment resulted in a significant improvement of survival time and pathological parameters in pigs with ischemic liver failure.
AuthorsShin Enosawa, Tomoyuki Miyashita, Tomohiro Saito, Takeshi Omasa, Toshiharu Matsumura (Affiliation: Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan. senosawa at nch.go.jp)
JournalCell transplantation (Cell Transplant) Vol. 15 Issue 10 Pg. 873-80 ( 2006) ISSN: 0963-6897 United States
PMID17299991 (Publication Type: Journal Article)
Chemical References
  • Glutamate-Ammonia Ligase
Topics
  • Animals
  • Bioreactors
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Transplantation
  • Cricetinae
  • Disease Models, Animal
  • Female
  • Glutamate-Ammonia Ligase (genetics, metabolism)
  • Humans
  • Liver Failure (metabolism, mortality, therapy)
  • Liver, Artificial
  • Male
  • Models, Biological
  • Survival Rate
  • Swine
  • Transfection