In vivo estimation of bioartificial liver with recombinant HepG2 cells using pigs with ischemic liver failure

Biological efficacy of a recombinant human hepatic cell line, glutamine syn thetase transfected HepG2 (GS-HepG2), was examined with large-scale culture in a circulatory flow bioreactor and in pigs with ischemic liver failure. GS-HepG2 cells were cultured in a circulatory flow bioreactor from 5 x 10(7 ) to 4 x 10(9) cells for 109 days, The cells showed ammonia removal activit y even under substrate (glutamic acid)-free medium, suggesting that the GS catalyzed the activity using intracellular glutamic acid that had been pool ed during conventional culture. When GS-HepG2 bioartificial liver (BAL) was applied to pigs with ischemic liver failure, survival time was prolonged t o 18.8 +/-6.1 h (mean +/- SD, n = 4) from 13.8 +/-5.4 h (n = 6) and 10.7 +/ -4.1 h (n = 6) (groups treated with cell-free BAL and treated with plasma e xchange and continuous hemodiafiltration, respectively). Laboratory data in dicated the tendency for improvement in increase of blood ammonia level and decline of blood coagulation indices in the GS-HepG2 BAL-treated group. Th e advantages and potential for the cell line as a bioreactor in BAL is also discussed, comparing to those of isolated porcine hepatocytes.