Extracorporeal Application of a Gel-Entrapment, Bioartificial Liver: Demonstration of Drug Metabolism and Other Biochemical Functions
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 hemope...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
1993-11-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/096368979300200602 |
| _version_ | 1819060447364513792 |
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| author | Scott L. 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 M.D. |
| author_facet | Scott L. 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 M.D. |
| author_sort | Scott L. Nyberg |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T14:27:08Z |
| format | Article |
| id | doaj.art-7cdc166c29d44087bc7f448ab05577a3 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-21T14:27:08Z |
| publishDate | 1993-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-7cdc166c29d44087bc7f448ab05577a32022-12-21T19:00:36ZengSAGE PublishingCell Transplantation0963-68971555-38921993-11-01210.1177/096368979300200602Extracorporeal Application of a Gel-Entrapment, Bioartificial Liver: Demonstration of Drug Metabolism and Other Biochemical FunctionsScott L. Nyberg0Ken Shirabe1Madhusudan V. Peshwa2Timothy D. Sielaff3Paul L. Crotty4Henry J. Mann5Rory P. Remmel6William D. Payne7Wei-Shou Hu8Frank B. Cerra M.D.Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USASecond Department of Surgery, Kyushu University, Fukuoka, 812, JapanDepartment of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USADepartment of Surgery, University of Minnesota, Minneapolis, MN 55455, USADepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USADepartment of Pharmacy Practice, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USADepartment of Surgery, University of Minnesota, Minneapolis, MN 55455, USADepartment of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USAMetabolic 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.https://doi.org/10.1177/096368979300200602 |
| spellingShingle | Scott L. 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 M.D. Extracorporeal Application of a Gel-Entrapment, Bioartificial Liver: Demonstration of Drug Metabolism and Other Biochemical Functions Cell Transplantation |
| title | Extracorporeal Application of a Gel-Entrapment, Bioartificial Liver: Demonstration of Drug Metabolism and Other Biochemical Functions |
| title_full | Extracorporeal Application of a Gel-Entrapment, Bioartificial Liver: Demonstration of Drug Metabolism and Other Biochemical Functions |
| title_fullStr | Extracorporeal Application of a Gel-Entrapment, Bioartificial Liver: Demonstration of Drug Metabolism and Other Biochemical Functions |
| title_full_unstemmed | Extracorporeal Application of a Gel-Entrapment, Bioartificial Liver: Demonstration of Drug Metabolism and Other Biochemical Functions |
| title_short | Extracorporeal Application of a Gel-Entrapment, Bioartificial Liver: Demonstration of Drug Metabolism and Other Biochemical Functions |
| title_sort | extracorporeal application of a gel entrapment bioartificial liver demonstration of drug metabolism and other biochemical functions |
| url | https://doi.org/10.1177/096368979300200602 |
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