Treatment of fulminant hepatic failure in rats using a bioartificial liver device containing porcine hepatocytes producing interleukin-1 receptor antagonist

Masahiro Shinoda, Arno W. Tilles, Go Wakabayashi, Atsushi Takayanagi, Hirohisa Harada, Hideaki Obara, Kazuhiro Suganuma, François Berthiaume, Motohide Shimazu, Nobuyoshi Shimizu, Masaki Kitajima, Ronald G. Tompkins, Mehmet Toner, Martin L. Yarmush

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Abstract

Fulminant hepatic failure (FHF) is a serious clinical condition that is associated with high mortality. There is evidence that FHF is an inflammatory disease, which is supported clinically by elevated serum levels of cytokines. In an effort to develop hepatocytes with additional functions for use in our bioartificial liver (BAL) device, we focused on interleukin-1 (IL-I) blockade as a therapeutic modality. Primary porcine hepatocytes were isolated from the livers of miniature swine and then transfected with an adenoviral vector encoding human interleukin-1 receptor antagonist (AdIL-IRa). The transfected hepatocytes secreted human IL-IRa. These transfected hepatocytes were incorporated into a flat-plate BAL device to evaluate their efficacy in treating D-galactosamine (GaIN)-induced FHF in a rat model. After extracorporeal perfusion with the BAL device containing the transfected hepatocytes, there were significant reductions in the plasma levels of hepatic enzymes (aspartate aminotransferase and alanine aminotransferase) and cytokines (IL-1 and IL-6), indicating a beneficial effect. Animal survival was significantly improved in the treated group compared to the control group. These experiments demonstrate that combining inflammatory cytokine blockade with a functional BAL device may be an effective therapeutic option in the treatment of FHF.

Original languageEnglish
Pages (from-to)1313-1323
Number of pages11
JournalTissue Engineering
Volume12
Issue number5
DOIs
Publication statusPublished - 2006 May 1

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ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Cell Biology

Cite this

Shinoda, M., Tilles, A. W., Wakabayashi, G., Takayanagi, A., Harada, H., Obara, H., Suganuma, K., Berthiaume, F., Shimazu, M., Shimizu, N., Kitajima, M., Tompkins, R. G., Toner, M., & Yarmush, M. L. (2006). Treatment of fulminant hepatic failure in rats using a bioartificial liver device containing porcine hepatocytes producing interleukin-1 receptor antagonist. Tissue Engineering, 12(5), 1313-1323. https://doi.org/10.1089/ten.2006.12.1313