Dynamic Model of Amino Acid and Carbohydrate Metabolism in Primary Human Liver Cells
Human liver cell bioreactors are used in extracorporeal liver support therapy. To optimize bioreactor operation with respect to clinical application an understanding of the central metabolism is desired. A two-compartment model consisting of a system of 48 differential equations was fitted to time series data of the concentrations of 18 amino acids, ammonia, urea, glucose, galactose, sorbitol and lactate, measured in the medium outflow of seven liver cell bioreactor runs. Using the presented model, the authors predict an amino acid secretion from proteolytic activities during the first day after inoculation of the bioreactor with primary liver cells. Furthermore, gluconeogenetic activites from amino acids and/or protein were predicted.
KeywordsLiver Support Human Liver Cell Inflow Stream Glucose Lactate Primary Liver Cell
Unable to display preview. Download preview PDF.
- 1.Gerlach, J.C., Zeilinger, K., Grebe, A., Puhl, G., Pless, G., Sauer, I., Grunwald, A., Schnoy, N., Muller, C., Neuhaus, P.: Recovery of preservation-injured primary human hepatocytes and nonparenchymal cells to tissuelike structures in large-scale bioreactors for liver support: an initial transmission electron microscopy study. J. Invest. Surg. 16, 83–92 (2003)CrossRefGoogle Scholar
- 2.Zeilinger, K., Holland, G., Sauer, I.M., Efimova, E., Kardassis, D., Obermayer, N., Liu, M., Neuhaus, P., Gerlach, J.C.: Time course of primary liver cell reorganization in three-dimensional high-density bioreactors for extracorporeal liver support: an immunohisto-chemical and ultrastructural study. Tissue Eng. 10, 1113–1124 (2004)Google Scholar
- 3.Pfaff, M., Toepfer, S., Woetzel, D., Driesch, D., Zeilinger, K., Pless, G., Neuhaus, P., Gerlach, J.C., Schmidt-Heck, W., Guthke, R.: Fuzzy cluster and rule based analysis of the system dynamics of a bioartificial 3D human liver cell bioreactor for liver support therapy. In: Dounias, G., Magoulas, G., Linkens, D. (eds.) Intelligent Technologies in Bioinformatics and Medicine. Special Session. Proceedings of the EUNITE 2004 Symposium. A Publication of the University of the Aegean, vol. 57 (2004)Google Scholar
- 4.Schmidt-Heck, W., Zeilinger, K., Pfaff, M., Toepfer, S., Driesch, D., Pless, G., Neuhaus, P., Gerlach, J.C., Guthke, R.: Network analysis of the kinetics of amino acid metabolism in a liver cell bioreactor. Lect. Notes Comput. Sc, vol. 3337, pp. 427–438. Springer, Heidelberg (2004)Google Scholar
- 5.Schmidt-Heck, W., Zeilinger, K., Pless, G., Gerlach, J.C., Pfaff, M., Guthke, R.: Prediction of the Performance of Human Liver Cell Bioreactors by Donor Organ Data. In: Oliveira, J.L., Maojo, V., Martín-Sánchez, F., Pereira, A.S. (eds.) ISBMDA 2005. LNCS (LNBI), vol. 3745, pp. 109–119. Springer, Heidelberg (2005)CrossRefGoogle Scholar
- 7.Kremling, A., Gilles, E.D.: Model based measurements for cell culture reactors. In: Conference on Systems Biology of Mammalian Cells, Heidelberg, July 12-14 (2006)Google Scholar