Extracorporeal application of a gel-entrapment, bioartificial liver: Demonstration of drug metabolism and other biochemical functions

Scott Nyberg, Ken Shirabe, Madhusudan V. Peshwa, Timothy D. Sielaff, Paul L. Crotty, Henry J. Mann, Rory P. Remmel, William D. Payne, Wei Shou Hu, Frank B. Cerra

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79 Scopus citations

Abstract

Metabolic activity of a gel-entrapment, hollow fiber, bioartificial liver was evaluated in vitro and during extracorporeal hemoperfusion in an anhepatic rabbit model. The bioartificial liver contained either 100 million rat hepatocytes (n = 12), fibroblasts (n = 3), or no cells (n = 7) during hemoperfusion of anhepatic rabbits. Eight other anhepatic rabbits were studied without hemoperfusion as anhepatic controls, and three sham rabbits served as normal controls. Albumin production rates (mean ± SEM) were similar during in vitro (17.0 ± 2.8 μg/h) and extracorporeal (18.0 ± 4.0 μg/h) application of the hepatocyte bioartificial liver. Exogenous glucose requirements were reduced (p < 0.01) and euglycemia was prolonged (p < 0.001) in anhepatic rabbits treated with the hepatocyte bioartificial liver. The maximum rate of glucose production by the hepatocyte bioartificial liver ranged from 50-80 μg/h. Plasma concentrations of aromatic amino acids, proline, alanine, and ammonia were normalized in anhepatic rabbits during hepatocyte hemoperfusion. Gel-entrapped hepatocytes in the bioartificial liver performed sulfation and glucuronidation of 4-methylumbelliferone. P450 activity was demonstrated during both in vitro and extracorporeal application of the BAL device by the formation of 3-hydroxy-lidocaine, the major metabolite of lidocaine biotransformation by gel-entrapped rat hepatocytes. In summary, a gel-entrapment, bioartificial liver performed multiple hepatocyte-specific functions without adverse side effects during extracorporeal application in an anhepatic, small animal model. With its potential for short term support of acute liver failure, scale-up of the current bioartificial liver device is indicated for further investigations in large animal, preclinical trials.

Original languageEnglish (US)
Pages (from-to)441-452
Number of pages12
JournalCell Transplantation
Volume2
Issue number6
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

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Keywords

  • Artificial organ
  • Bioartificial liver
  • Drug metabolism
  • Hepatocyte

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

Cite this

Nyberg, S., Shirabe, K., Peshwa, M. V., Sielaff, T. D., Crotty, P. L., Mann, H. J., Remmel, R. P., Payne, W. D., Hu, W. S., & Cerra, F. B. (1993). Extracorporeal application of a gel-entrapment, bioartificial liver: Demonstration of drug metabolism and other biochemical functions. Cell Transplantation, 2(6), 441-452. https://doi.org/10.1177/096368979300200602