Cytotoxic immune response to a xenogeneic bioartificial liver

Scott L. Nyberg, Bruce Amiot, Joseph Hardin, Edwina Baskin-Bey, Jeffrey L. Platt

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Prior studies have suggested the possibility of immune-mediated death of xenogeneic hepatocytes in a bioartificial liver (BAL) during hemoperfusion. This study was designed to elucidate how immunity may cause death of xenogeneic hepatocytes in the BAL. Healthy dogs were treated with a BAL containing hollow fiber membranes with large pores (200 nm) or small pores (400 kDa), The immune response of recipient dogs to BAL therapy was monitored over 3 h of treatment. We observed significantly greater loss of viability of hepatocytes in the 200 nm group compared with the 400 kDa group (p < 0.001), Low viability after treatment with the large pore membrane was associated with positive staining for dog IgG, dog IgM, and dog complement on dead hepatocytes. Significant levels of dog antibody were detected in samples of BAL medium from the 200 nm group. These canine antibodies were cytotoxic to porcine hepatocytes. In contrast, medium from the 400 kDa group contained only trace levels of dog IgG and were noncytotoxic. We conclude that antibody-mediated cytotoxicity contributed to the death of hepatocytes during treatment with a xenogeneic BAL. Immune-mediated death of hepatocytes was reduced by increasing selectivity of the BAL membrane.

Original languageEnglish (US)
Pages (from-to)783-791
Number of pages9
JournalCell transplantation
Volume13
Issue number7-8
DOIs
StatePublished - 2004

Keywords

  • Bioartificial liver
  • Porcine hepatocyte
  • Xenoreactive antibody

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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