Development of a bioartificial liver employing xenogeneic hepatocytes.

Cytotechnology
W S HuF B Cerra

Abstract

Liver failure is a major cause of mortality. A bioartificial liver (BAL) employing isolated hepatocytes can potentially provide temporary support for liver failure patients. We have developed a bioartificial liver by entrapping hepatocytes in collagen loaded in the luminal side of a hollow fiber bioreactor. In the first phase of development, liver-specific metabolic activities of biosynthesis, biotransformation and conjugation were demonstrated. Subsequently anhepatic rabbits were used to show that rat hepatocytes continued to function after the BAL was linked to the test animal. For scale-up studies, a canine liver failure model was developed using D-galactosamine overdose. In order to secure a sufficient number of hepatocytes for large animal treatment, a collagenase perfusion protocol was established for harvesting porcine hepatocytes at high yield and viability. An instrumented bioreactor system, which included dissolved oxygen measurement, pH control, flow rate control, an oxygenator and two hollow fiber bioreactors in series, was used for these studies. An improved survival of dogs treated with the BAL was shown over the controls. In anticipated clinical applications, it is desirable to have the liver-specific activities ...Continue Reading

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Citations

Apr 4, 2001·Artificial Organs·K FunatsuK Sugimachi
Nov 10, 2001·Annual Review of Biomedical Engineering·E S TzanakakisW S Hu
Oct 20, 2005·Journal of Bioscience and Bioengineering·Jung-Keug Park, Doo-Hoon Lee
Apr 13, 2010·Expert Opinion on Drug Metabolism & Toxicology·Qin Meng
Jan 28, 2016·Regenerative Biomaterials·Dongyuan LüMian Long
Sep 20, 2018·Advanced Healthcare Materials·Cécile LegallaisDimitrios Stamatialis
Oct 22, 2004·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Christina ChanMartin L Yarmush
Apr 26, 2007·Macromolecular Bioscience·Aysel KoçY Murat Elçin
Jan 14, 2005·The International Journal of Artificial Organs·J l FukudaK Funatsu
Apr 19, 2005·Biotechnology and Bioengineering·Jaesung ParkArno W Tilles

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