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

Abstract

We 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.

• Authors: Shin Enosawa, Tomoyuki Miyashita, Tomohiro Saito, Takeshi Omasa, Toshiharu Matsumura
• Journal: Cell transplantation (Cell Transplant) Vol. 15 Issue 10 Pg. 873-80 ( 2006) ISSN: 0963-6897 [Print] United States
• PMID: 17299991 (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