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A Single Dynamic Metabolic Model Can Describe mAb Producing CHO Cell Batch and Fed-Batch Cultures on Different Culture Media

Julien Robitaille, Jingkui Chen and Mario Jolicoeur

Article (2015)

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CHO cell culture high productivity relies on optimized culture medium management under fed-batch or perfused chemostat strategies enabling high cell densities. In this work, a dynamic metabolic model for CHO cells was further developed, calibrated and challenged using datasets obtained under four different culture conditions, including two batch and two fed-batch cultures comparing two different culture media. The recombinant CHO-DXB11 cell line producing the EG2-hFc monoclonal antibody was studied. Quantification of extracellular substrates and metabolites concentration, viable cell density, monoclonal antibody concentration and intracellular concentration of metabolite intermediates of glycolysis, pentose-phosphate and TCA cycle, as well as of energetic nucleotides, were obtained for model calibration. Results suggest that a single model structure with a single set of kinetic parameter values is efficient at simulating viable cell behavior in all cases under study, estimating the time course of measured and non-measured intracellular and extracellular metabolites. Model simulations also allowed performing dynamic metabolic flux analysis, showing that the culture media and the fed-batch strategies tested had little impact on flux distribution. This work thus paves the way to an in silico platform allowing to assess the performance of different culture media and fed-batch strategies.

Uncontrolled Keywords

Amino Acids; Animals; Antibodies, Monoclonal; Batch Cell Culture Techniques; Biotechnology; CHO Cells; Cricetulus; Culture Media; Energy Metabolism; Glycolysis; Metabolic Networks and Pathways; Models, Biological; Amino Acids; Antibodies, Monoclonal; Culture Media

Subjects: 1800 Chemical engineering > 1800 Chemical engineering
1900 Biomedical engineering > 1900 Biomedical engineering
Department: Department of Chemical Engineering
Funders: CRSNG / NSERC, Canada Research Chair program, Monoclonal Antibody Network (MabNet)
Grant number: NETGP380070-08, 950-201896
PolyPublie URL: https://publications.polymtl.ca/3485/
Journal Title: PLOS One (vol. 10, no. 9)
Publisher: PLOS
DOI: 10.1371/journal.pone.0136815
Official URL: https://doi.org/10.1371/journal.pone.0136815
Date Deposited: 23 Nov 2018 10:08
Last Modified: 08 Apr 2024 13:57
Cite in APA 7: Robitaille, J., Chen, J., & Jolicoeur, M. (2015). A Single Dynamic Metabolic Model Can Describe mAb Producing CHO Cell Batch and Fed-Batch Cultures on Different Culture Media. PLOS One, 10(9). https://doi.org/10.1371/journal.pone.0136815


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