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Selection of chemically defined media for CHO cell fed-batch culture processes
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cell line and producing the same monoclonal antibody (BC-G, a low producing clone; BC-P, a high producing clone) were tested in four basal media in all possible combinations with three feeds (=12 conditions) in fed-batch cultures. Higher amino acid feeding did not always lead to higher mAb production. The two clones showed differences in cell physiology, metabolism and optimal medium-feed combinations. During the phase transitions of all cultures, cell metabolism showed a shift represented by lower specific consumption and production rates, except for the specific glucose consumption rate in cultures fed by Actifeed A/B. The BC-P clone fed by Actifeed A/B showed a threefold cell volume increase and an increase of the specific consumption rate of glucose in the stationary phase. Since feeding was based on glucose this resulted in accumulation of amino acids for this feed, while this did not occur for the poorer feed (EFA/B). The same feed also led to an increase of cell size for the BC-G clone, but to a lesser extent.
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Other studies show that the absence of media components such as amino acids can trigger growth arrest due to nutrient depletion.
“Other studies show that the absence of media components such as amino acids can also trigger growth arrest due to nutrient depletion.[12,21]”
From Biomass specific perfusion rate as a control lever for the continuous manufacturing of biosimilar monoclonal antibodies from CHO cell cultures (2024) · cites this paper as [12]
The Discussion (Effects of media and feed on culture performances and cell physiology; page not provided) suggests that depletion of certain nutrients might have caused cell-cycle arrest, but presents this as one possibility rather than a demonstrated cause. The Discussion (Cell metabolism and feed composition; page not provided) reports that glutamine and asparagine depletion coincided with a shift to stationary phase, while saying the effect of non-essential amino-acid depletion could not be confirmed in this study. (LLM, conf=0.87)
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Cites
Production of recombinant protein therapeutics in cultivated mammalian cells
Wurm, F. M. (2004) · Nature Biotechnology · doi:10.1038/nbt1026 · Cited by 2,032
Lao, M.-S., & Toth, D. (1997) · Biotechnology Progress · doi:10.1021/bp9602360 · Cited by 268
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Research works printed but not linked: 29
- Ahn WS, Antoniewicz MR (2011) Metabolic flux analysis of CHO cells at growth and non-growth phases using isotopic tracers and mass spectrometry. Metab Eng 13:598–609 · DOI
- Bi JX, Shuttleworth J, Al-Rubeai M (2004) Uncoupling of cell growth and proliferation results in enhancement of productivity in p21CIP1-arrested CHO cells. Biotechnol Bioeng 85:741–749 · DOI
- Carvalhal A, Marcelino I, Carrondo M (2003) Metabolic changes during cell growth inhibition by p27 overexpression. Appl Microbiol Biotechnol 63:164–173 · DOI
- Chen P, Harcum SW (2005) Effects of amino acid additions on ammonium stressed CHO cells. J Biotechnol 117:277–286 · DOI
- Costa AR, Withers J, Rodrigues ME, McLoughlin N, Henriques M, Oliveira R, Rudd PM, Azeredo J (2013) The impact of cell adaptation to serum-free conditions on the glycosylation profile of a monoclonal antibody produced by Chinese hamster ovary cells. N Biotechnol 30:563–572 · DOI
- Fomina-Yadlin D, Gosink JJ, McCoy R, Follstad B, Morris A, Russell CB, McGrew JT (2014) Cellular responses to individual amino-acid depletion in antibody-expressing and parental CHO cell lines. Biotechnol Bioeng 111:965–979 · DOI
- Hansen HA, Emborg C (1994) Influence of ammonium on growth, metabolism, and productivity of a continuous suspension Chinese hamster ovary cell culture. Biotechnol Prog 10:121–124 · DOI
- Hoffmann EK, Lambert IH, Pedersen SF (2009) Physiology of cell volume regulation in vertebrates. Physiol Rev 89:193–277 · DOI · Paper page
- Hossler P, Khattak SF, Li ZJ (2009) Optimal and consistent protein glycosylation in mammalian cell culture. Glycobiology 19:936–949 · DOI
- Kim TK, Chung JY, Sung YH, Lee GM (2001) Relationship between cell size and specific thrombopoietin productivity in Chinese hamster ovary cells during dihydrofolate reductase-mediated gene amplification. Biotechnol Bioprocess Eng 6:332–336 · DOI · Paper page
- Kishishita S, Katayama S, Kodaira K, Takagi Y, Matsuda H, Okamoto H, Takuma S, Hirashima C, Aoyagi H (2015) Optimization of chemically defined feed media for monoclonal antibody production in Chinese hamster ovary cells. J Biosci Bioeng 120:78–84 · DOI
- Kyriakopoulos S, Kontoravdi C (2014) A framework for the systematic design of fed-batch strategies in mammalian cell culture. Biotechnol Bioeng 111:2466–2476 · DOI
- Li J, Wong CL, Vijayasankaran N, Hudson T, Amanullah A (2012) Feeding lactate for CHO cell culture processes: impact on culture metabolism and performance. Biotechnol Bioeng 109:1173–1186 · DOI · Paper page
- Lloyd DR, Holmes P, Jackson LP, Emery AN, Al-Rubeai M (2000) Relationship between cell size, cell cycle and specific recombinant protein productivity. Cytotechnology 34:59–70 · DOI · Paper page
- Luo J, Vijayasankaran N, Autsen J, Santuray R, Hudson T, Amanullah A, Li F (2012) Comparative metabolite analysis to understand lactate metabolism shift in Chinese hamster ovary cell culture process. Biotechnol Bioeng 109:146–156 · DOI
- Ma N, Ellet J, Okediadi C, Hermes P, McCormick E, Casnocha S (2009) A single nutrient feed supports both chemically defined NS0 and CHO fed-batch processes: improved productivity and lactate metabolism. Biotechnol Prog 25:1353–1363 · DOI
- Martínez VS, Dietmair S, Quek LE, Hodson MP, Gray P, Nielsen LK (2013) Flux balance analysis of CHO cells before and after a metabolic switch from lactate production to consumption. Biotechnol Bioeng 110:660–666 · DOI
- Martínez VS, Buchsteiner M, Gray P, Nielsen LK, Quek L-E (2015) Dynamic metabolic flux analysis using B-splines to study the effects of temperature shift on CHO cell metabolism. Metab Eng Commun 2:46–57 · DOI
- Mulukutla BC, Gramer M, Hu W-S (2012) On metabolic shift to lactate consumption in fed-batch culture of mammalian cells. Metab Eng 14:138–149 · DOI
- Oh SK, Chua FK, Choo AB (1995) Intracellular responses of productive hybridomas subjected to high osmotic pressure. Biotechnol Bioeng 46:525–535 · DOI
- Read EK, Bradley SA, Smitka TA, Agarabi CD, Lute SC, Brorson KA (2013) Fermentanomics informed amino acid supplementation of an antibody producing mammalian cell culture. Biotechnol Prog 29:745–753 · DOI
- Reinhart D, Damjanovic L, Kaisermayer C, Kunert R (2015) Benchmarking of commercially available CHO cell culture media for antibody production. Appl Microbiol Biotechnol 99:4645–4657 · DOI
- Renner W, Jordan M, Eppenberger H, Leist C (1993) Cell–cell adhesion and aggregation: influence on the growth behavior of CHO cells. Biotechnol Bioeng 41:188–193 · DOI
- Rodrigues ME, Costa AR, Henriques M, Azeredo J, Oliveira R (2012) Comparison of commercial serum-free media for CHO-K1 cell growth and monoclonal antibody production. Int J Pharm 437:303–305 · DOI
- Yang M, Butler M (2000) Effects of ammonia on CHO cell growth, erythropoietin production, and glycosylation. Biotechnol Bioeng 68:370–380 · DOI
- Young JD (2013) Metabolic flux rewiring in mammalian cell cultures. Curr Opin Biotechnol 24:1108–1115 · DOI
- Yu M, Hu Z, Pacis E, Vijayasankaran N, Shen A, Li F (2011) Understanding the intracellular effect of enhanced nutrient feeding toward high titer antibody production process. Biotechnol Bioeng 108:1078–1088 · DOI
- Zagari F, Stettler M, Baldi L, Broly H, Wurm FM, Jordan M (2013) High expression of the aspartate-glutamate carrier Aralar1 favors lactate consumption in CHO cell culture. Pharma Bioprocess 1:19–27 · DOI
- Zamorano F, Wouwer AV, Bastin G (2010) A detailed metabolic flux analysis of an underdetermined network of CHO cells. J Biotechnol 150:497–508 · DOI
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Pérez-Rodriguez, S., Ramírez-Lira, M. D. J., Trujillo-Roldán, M. A., & Valdez-Cruz, N. A. (2020) · Bioengineered · doi:10.1080/21655979.2020.1744266 · Cited by 32
Transcriptome Analysis of CHO Cell Size Increase During a Fed-Batch Process
Pan, X., Alsayyari, A. A., Dalm, C., Hageman, J. A., Wijffels, R. H., & Martens, D. E. (2019) · Biotechnology Journal · doi:10.1002/biot.201800156 · Cited by 22
Self-citationLeong, J., Tang, W. Q., Chng, J., Ler, W. X., Manan, N. A., Sim, L. C., Zheng, Z. Y., Zhang, W., Walsh, I., Zijlstra, G., et al. (2024) · Biotechnology Journal · doi:10.1002/biot.202400092 · Cited by 9
“[12] Therefore, the precision of pro-cesscontrolsmightbeimprovedwhentheincreasingcellvolumeisalso considered.”
Influential
Metadata
- Authors
- Pan, X., Streefland, M., Dalm, C., Wijffels, R. H., & Martens, D. E.
- Affiliations
- Wageningen University & Research (NL)
- Synthon (Netherlands) (NL)
- Nord University (NO)
- Corresponding author
- Pan, Xiao
- Venue
- Cytotechnology
- Published
- 2016-11-29
- Volume
- 69
- Issue
- 1
- Pages
- 39-56
- ISSN
- 0920-9069 (ISSN-L)
- 1573-0778
- PMC
- PMC5264622
- OpenAlex
- W2557685022
- Cited by
- 70
- References
- 2
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 15 · 2020: 5 · 2019: 11 · 2018: 8 · 2017: 1 · 2016: 1
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cytotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion, cc-by)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Funders
- European Regional Development Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Keywords
- CHO cell culture, fed-batch fermentation, chemically defined medium, monoclonal antibody production, amino acid supplementation, glucose feeding, cellular metabolism, glucose consumption rate, cell growth, cell size, cell line differences
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