Genomic Biochemical Engineering
| | Cell Culture Engineering
| Metabolic
Pathway Engineering
| Liver Cell Self Assembly
| Analysis
of Bioreaction Network | Stem
Cell Culture Engineering | Image
Processing in Fluorescence Microscopy | Bioartificial
Liver | MAIN
RESEARCH PAGE
The University of Minnesota Bioartificial LiverResults:In the first phase of development, liver-specific activities of biosynthesis, biotransformation and conjugation were demonstrated. Subsequently, anhepatic rabbits were used to show that 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. Two groups of injured animals were studied, one which received BAL treatment, and one which did not. Uninjured dogs served as a control. The survival of dogs treated with the BAL was higher than the controls dogs that did not receive BAL treatment, as shown in the figure below. Based on these results, FDA approval was given for Phase I human clinical trials, which are slated to begin in later this year.
For anticipated clinical applications, it is desirable to further increase the liver-specific activities in the BAL. To that end, the possibility of employing hepatocyte spheroids in the BAL was explored. These self-assembled spheroids formed from monolayer culture exhibit higher liver-specific functions and remained viable longer than hepatocytes in a monolayer. Collagen entrapment of these spheroids resulted in sustaining their liver-specific functions at higher levels even longer than those maintained in suspension. Liver-specific function was 2-5 fold higher in the spheroid BAL than in a BAL containing isolated hepatocytes. Application of spheroids in a BAL is under further investigation. For more information on hepatocyte spheroids, please see our liver self-assembly web page. |
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Tzanakakis, E. S., Hess, D. J., Sielaff, T. D., and Hu, W. S. (2000) Extracorporeal tissue engineered liver-assist devices, Annu. Rev. Biomed. Eng. 2:607-32. |
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Friend, J.R. and Hu, W.S. (1998) Engineering a Bioartificial Liver Support. In Tissue Engineering: Fundamentals and Concepts, C. W. Patrick, A. G. Mikos and L. V. McIntire, eds. (Elsevier Science), pp. 678-690. |
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Hu, W.S., Friend, J.R., Wu, F.J., Sielaff, T., Peshwa, M.V., Lazar, A., Nyberg, S.L, Hansen, L.K., Remmel, R.P. and Cerra, F.B. (1997) Development of a bioartificial liver employing xenogeneic hepatocytes, Cytotechnology, 23, 29-38. |
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Wu, F.J., Friend, J.R., Lazar, A., Mann, H.J., Remmel, R.P., Cerra, F.B., and Hu, W.S. (1996) Hollow fiber bioartificial liver utilizing collagen entrapped porcine hepatocyte spheroids, Biotechnology and Bioengineering, 52, 34-44. |
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Sielaff, T.D., Hu, M.Y., Amiot, B., Rollins, M.D., Rao, S., McGuire, B., Bloomer, J.R., Hu, W.S., and Cerra, F.B. (1995) Gel-entrapment bioartificial liver therapy in galactosamine hepatitis, Journal of Surgical Research, 59, 179-184. |
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Wu, F.J., Peshwa, M.V., Cerra, F.B., and Hu, W.S. (1995) Entrapment of hepatocyte spheroids in a hollow fiber bioreactor as a potential bioartificial liver, Tissue Engineering, 1, 29-40. |
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Nyberg, S.L, Shirabe, K., Peshwa, M.V., Sielaff, T.D., Crotty, R.L., Mann, H.J., Remmel, R.P., Payne, W.D., Hu, W.S., and Cerra, F.B. (1993) Extra-corporeal application of a gel-entrapment bioartificial liver: Demonstration of drug metabolism and other biochemical functions, Cell Transplantation, 2, 441-452. |
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Nyberg, S.L., Shatford, R., Peshwa, M.V., White, J.G., Cerra, F.B., and Hu, W.S. (1993) Evaluation of a hepatocyte entrapment hollow fiber bioreactor: a potential bioartificial liver, Biotechnology and Bioengineering, 41, 194-203. |
