ArticleBiotechnology and bioengineering2021
Application of metabolic modeling for targeted optimization of high seeding density processes.
Article in Biotechnology and bioengineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 21 citations in OpenAlex.
- Cell specific perfusion rates drive growth dynamics and metabolism in CHO N-1 perfusion processes independent of perfusion rate control method.Frontiers in bioengineering and biotechnology · 2025Article
- Building blocks needed for mechanistic modeling of bioprocesses: A critical review based on protein production by CHO cells.Metabolic engineering communications · 2024Review
- Deciphering Metabolic Pathways in High-Seeding-Density Fed-Batch Processes for Monoclonal Antibody Production: A Computational Modeling Perspective.Bioengineering (Basel, Switzerland) · 2024Article
- Rapid intensification of an established CHO cell fed-batch process.Biotechnology progress · 2022Article
- Generic and specific recurrent neural network models: Applications for large and small scale biopharmaceutical upstream processes.Biotechnology reports (Amsterdam, Netherlands) · 2021Article
- From omics to Cellular mechanisms in mammalian cell factory development.Current opinion in chemical engineering · 2021Article
- Application of metabolic modeling for targeted optimization of high seeding density processes.Biotechnology and bioengineering · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Process intensification by application of perfusion mode in pre-stage bioreactors and subsequent inoculation of cell cultures at high seeding densities (HSD) has the potential to meet the increasing requirements of future manufacturing demands. However, process development is currently restrained by a limited understanding of the cell's requirements under these process conditions. The goal of this study was to use extended metabolite analysis and metabolic modeling for targeted optimization of HSD cultivations. The metabolite analysis of HSD N-stage cultures revealed accumulation of inhibiting metabolites early in the process and flux balance analysis led to the assumption that reactive oxygen species (ROS) were contributing to the fast decrease in cell viability. Based on the metabolic analysis an optimized feeding strategy with lactate and cysteine supplementation was applied, resulting in an increase in antibody titer of up to 47%. Flux balance analysis was further used to elucidate the surprisingly strong synergistic effect of lactate and cysteine, indicating that increased lactate uptake led to reduced ROS formation under these conditions whilst additional cysteine actively reduced ROS via the glutathione pathway. The presented results finally demonstrate the benefit of modeling approaches for process intensification as well as the potential of HSD cultivations for biopharmaceutical manufacturing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.