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The Significant Improvement of Survival Times and Pathological Parameters by Bioartificial Liver With Recombinant HepG2 in Porcine Liver Failure Model

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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.

Keywords: Bioartificial liver (BAL); HepG2; Ischemic liver failure; Porcine hepatocytes

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000006783981350

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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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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