Development of a mathematical model for evaluating the dynamics of normal and apoptotic Chinese hamster ovary cells |
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Authors: | Naderi Saeideh Meshram Mukesh Wei Catherine McConkey Brendan Ingalls Brian Budman Hector Scharer Jeno |
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Institution: | Dept. of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada N2L 3G1. |
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Abstract: | A metabolic flux based methodology was developed for modeling the metabolism of a Chinese hamster ovary cell line. The elimination of insignificant fluxes resulted in a simplified metabolic network which was the basis for modeling the significant metabolites. Employing kinetic rate expressions for growing and non-growing subpopulations, a logistic model was developed for cell growth and dynamic models were formulated to describe culture composition and monoclonal antibody (MAb) secretion. The model was validated for a range of nutrient concentrations. Good agreement was obtained between model predictions and experimental data. The ultimate goal of this study is to establish a comprehensive dynamic model which may be used for model-based optimization of the cell culture for MAb production in both batch and fed-batch systems. |
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Keywords: | CHO metabolic flux analysis apoptosis mathematical modeling logistic equation |
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