Model-based identification of cell-cycle-dependent metabolism and putative autocrine effects in antibody producing CHO cell culture

Biotechnology and Bioengineering
Johannes MöllerUwe Jandt

Abstract

The understanding of cell-cycle-dependent population heterogeneities in mammalian cell culture and their influence on production rates is still limited. Furthermore, metabolic regulations arising from self-expressed signaling factors (autocrine/autoinhibitory factors) have been postulated in the past, but no determination of such effects have been made so far for fast-growing production Chinese hamster ovary (CHO) cells in chemically defined media. In this study, a novel approach combining near-physiological treatment of cells (including synchronization), population resolved mechanistic modeling and statistical analysis was developed to identify population inhomogeneities. Cell-cycle-dependent population dynamics and metabolic regulations due to a putative autocrine factor were examined and their impact on the metabolic rates and antibody production of near-physiologically synchronized CHO DP-12 cell cultures was determined. To achieve this, a population resolved model was extended to describe putative autocrine-dependentt and cell-cycle-related metabolic rates for glucose, glutamine, lactate, ammonia, and antibody production. The model parameters were estimated based on data of two repeated batch cultivations (three batches ea...Continue Reading

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Citations

Feb 27, 2019·Bioprocess and Biosystems Engineering·Johannes MöllerRalf Pörtner
Jul 26, 2019·Biotechnology and Bioengineering·Johannes MöllerUwe Jandt
Jan 21, 2021·Bioprocess and Biosystems Engineering·André MoserJohannes Möller
Mar 16, 2021·Engineering in Life Sciences·Johannes MöllerAn-Ping Zeng
Apr 5, 2021·Metabolic Engineering·Conor M O'BrienWei-Shou Hu

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