Macroscopic Dynamic Modeling of Metabolic Shift to Lactate Consumption of Mammalian Cell Batch Cultures

A macroscopic model that considers the shift to lactate consumption is proposed to simulate the therapeutic proteins produced by mammalian cells using human embryonic kidney 293 cells (HEK293-6E) cultures. The macroscopic model contains four macroscopic reactions: (i) substrate consumption and lacta...

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Bibliographic Details
Main Authors: Pimentel, Guilherme A., Dewasme, Laurent, Santos-Navarro, Fernando N., Boes, Adrien, Cote, Francois, Filee, Patrice, Wouwer, Alain Vande
Format: Conference Proceeding
Language:English
Subjects:
Biological system modeling
Biomass
Glucose
Predictive models
Production
Proteins
Sensitivity analysis
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Summary:A macroscopic model that considers the shift to lactate consumption is proposed to simulate the therapeutic proteins produced by mammalian cells using human embryonic kidney 293 cells (HEK293-6E) cultures. The macroscopic model contains four macroscopic reactions: (i) substrate consumption and lactate production, (ii) lactate consumption, (iii) biomass death, and (iv) viable biomass maintenance. The maximum likelihood principal component analysis has been used to extract the number of reactions from experimental data collected in four batch experiments. The model parameters and confidence intervals are obtained via nonlinear least-squares identification. The model successfully predicts the dynamic behavior of cell growth and death, substrate consumption (glucose and glutamine), lactate production and consumption, and protein production. In addition, the proposed model structure is also validated as a generalized representation of the mammalian cell cultures that do not present lactate consumption.
ISSN:2576-3555
DOI:10.1109/CoDIT58514.2023.10284210