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

PloS One
Julien RobitailleMario Jolicoeur

Abstract

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 f...Continue Reading

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Apr 4, 2017·Biotechnology Journal·Wolfgang SommereggerGerald Striedner
Oct 14, 2017·Biotechnology Journal·Sarantos KyriakopoulosDong-Yup Lee
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Methods Mentioned

BETA
Assay
enzyme-linked immunosorbent assay
glycosylation

Software Mentioned

lsqcurvefit
MATLAB
MATLAB ToolBox

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