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

• Published in: Cell transplantation Vol. 15; no. 10; p. 873
• Main Authors: Enosawa, Shin, Miyashita, Tomoyuki, Saito, Tomohiro, Omasa, Takeshi, Matsumura, Toshiharu
• Format: Journal Article
• Language: English
• Published: United States SAGE Publishing 01-01-2006
• Subjects: Animals; Bioreactors; Cell Culture Techniques; Cell Line, Tumor; Cell Transplantation; Cricetinae; Disease Models, Animal; Female; Glutamate-Ammonia Ligase - genetics; Glutamate-Ammonia Ligase - metabolism; Humans; Liver Failure - metabolism; Liver Failure - mortality; Liver Failure - therapy; Liver, Artificial; Male; Models, Biological; Survival Rate; Swine; Transfection
• ISSN: 0963-6897; 1555-3892
• DOI: 10.3727/000000006783981350

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.