Population-based modeling of the progression of apoptosis in mammalian cell culture |
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Authors: | Meshram Mukesh Naderi Saeideh McConkey Brendan Budman Hector Scharer Jeno Ingalls Brian |
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Institution: | Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada. |
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Abstract: | The production of biopharmaceuticals from mammalian cell culture is hindered by apoptosis, which is the primary cause of cell death in these cultures. As a tool for optimization of culture yield, this study presents a population-based model describing the progression of apoptosis in a monoclonal antibody (mAb)-producing Chinese hamster ovary (CHO) cell culture. Because mAb production does not cease when apoptosis begins, the model was designed to incorporate subpopulations at various stages in the progression of apoptosis. The model was validated against intracellular measurements of caspase activity as well as cell density, nutrient levels, and toxic metabolites. Since the specific details of apoptotic mechanisms have not been elucidated in this cell line, we employed a model comparison analysis that suggests the most plausible pathways of activation. |
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Keywords: | apoptosis mathematical modeling mammalian cell culture Chinese hamster ovary monoclonal antibody |
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