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Cited by 79Viral Infectious Diseases and Gene Expression in InsectsFluid Dynamics and MixingMonoclonal and Polyclonal Antibodies Research

The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.

Effects of CO2 and osmolality on hybridoma cells: growth, metabolism and monoclonal antibody production

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deZengotita, Vivian M., Kimura, Roy, Miller, William M.·1998·Cytotechnology
DOI 10.1023/a:1008010605287PMC PMC3449846
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Abstract

CO2 partial pressure (pCO2) in industrial cell culture reactors may reach 150-200 mm Hg, which can significantly inhibit cell growth and recombinant protein production. Due to equilibrium with bicarbonate, increased pCO2 at constant pH results in a proportional increase in osmolality. Hybridoma AB2-143.2 cell growth rate decreased with increasing pCO2 in well-plate culture, with a 45% decrease at 195 mm Hg with partial osmolality compensation (to 361 mOsm kg- 1). Inhibition was more extensive without osmolality compensation, with a 63% decrease in growth rate at 195 mm Hg and 415 mOsm kg-1. Also, the hybridoma death rate increased with increasing pCO2, with 31- and 64-fold increases at 250 mm Hg pCO2 for 401 and 469 mOsm kg- 1, respectively. The specific glucose consumption and lactate production rates were 40-50% lower at 140 mm Hg pCO2. However, there was little further inhibition of glycolysis at higher pCO2. The specific antibody production rate was not significantly affected by pCO2 or osmolality within the range tested. Hybridomas were also exposed to elevated pCO2 in continuous culture. The viable cell density decreased by 25-40% at 140 mm Hg. In contrast to the well-plate cultures, the death rate was lower at the new steady state at 140 mm Hg. This was probably due to higher residual nutrient and lower byproduct levels at the lower cell density (at the same dilution rate), and was associated with increased cell-specific glucose and oxygen uptake. Thus, the apparent effects of pCO2 may vary with the culture system.

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  • In CO2 controlled cultures, controlling pH to a set point can result in a heavy CO2 burden on the cells, resulting in decreased culture performance in CHO cells and other cell types, including hybridoma cells.

    “In CO2 controlled cultures, controlling pH to a set point can result in a heavy CO2 burden on the cells, resulting in decreased culture performance in CHO cells as well as other cell types, including hybridoma cells. 15 , 16 , 17”

    From Dynamic pH profiles drive higher cell‐specific and volumetric productivity (2026) · cites this paper as [17]

    The Introduction reports that CO₂ can accumulate in bioreactors and inhibit CHO cell growth and production; the reported hybridoma experiments also show reduced growth at elevated pCO₂. But the paper attributes CO₂ accumulation to aeration conditions, not to controlling pH at a set point. Its Bioreactor experiments section says instead that elevated pCO₂ required more NaOH to maintain constant pH. (LLM, conf=0.84)

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Research works printed but not linked: 2

  1. Aunins JG, Glazomitsky K and Buckland B (1993) Animal Cell Culture Reactor Design: Known and Unknown. In: Proceedings of 3rd Intl. Conference on Bioreactor and Bioprocess Fluid Dynamics, Kluwer Academic Publishers, p. 175.
  2. Kimura, R (1996) Effects of elevated carbon dioxide partial pressure on recombinant Chinese hamster ovary and hybridoma cell cultures. PhD Dissertation, Northwestern University.

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Metadata

Authors
deZengotita, V. M., Kimura, R., & Miller, W. M.
Affiliations
Northwestern University (US)
Corresponding author
Miller, William M.
ORCID
Miller, William M.
Venue
Cytotechnology
Publisher
Springer Science and Business Media LLC
Published
1998-11
Volume
28
Issue
1-3
Pages
213-227
ISSN
  • 0920-9069 (ISSN-L)
  • 1573-0778
DOI
10.1023/a:1008010605287
PMC
PMC3449846
OpenAlex
W1513373195
Cited by
78
References
21
Citations by year
2026: 3 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 6 · 2017: 1 · 2016: 5 · 2015: 5 · 2014: 7 · 2013: 1
FWCI
0.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Cytotechnology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation (9402030)
  • National Institutes of Health
  • National Institute of General Medical Sciences (T32GM008449)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
  • Physical Sciences › Chemical Engineering › Fluid Flow and Transfer Processes › Fluid Dynamics and Mixing
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Keywords
hybridoma, monoclonal antibody production, cell growth inhibition, cell death rate, glucose utilization, lactic acid production, glycolysis, continuous culture, oxygen consumption

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