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 × 109 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.
Document Type: Research Article
Affiliations: 1: Department of Innovative Surgery, National Research Institute for Child Health and Development , Tokyo, Japan 2: Epidemiology, National Research Institute for Child Health and Development, Tokyo, Japan 3: Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, Japan 4: Roman Industries, Yokohama City, Japan
Publication date: October 1, 2006
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