Cited by 99Viral Infectious Diseases and Gene Expression in InsectsProtein purification and stabilityFungal and yeast genetics research

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Relationship between cell size, cell cycle and specific recombinant protein productivity

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Lloyd, David R., Holmes, Paul, Jackson, Lee P., Emery, A. Nicholas, Al-Rubeai, Mohamed·2000·Cytotechnology

DOI 10.1023/a:1008103730027PMC PMC3449736

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Abstract

Centrifugal elutriation was used to produce cell cycle enrichedfractions of four commercially relevant recombinant cell lines,chosen to allow for variation in properties due to construct,expression system and parent cell type, from normally growingheterogeneous batch cultures. As these fractions had identicalculture histories and had not been subjected to any insult orstress which was likely to have adversely affected cellularmetabolism, they were ideal for further study of cellularproperties. Specific productivity, cell size and cell cyclestate of replicate elutriated fractions were measured for eachcell line. Results showed that cell size was the major cellulardeterminant of productivity for all cell lines examined. Productformation was not restricted to any particular cell cycle phaseand in all cases, production occurred irrespective of cell cyclephase. Specific productivity was lowest when the majority ofcells in the fraction were G(1), intermediate when themajority of cells in the fraction were S phase and greater whenthe majority of cells in the fraction were in G(2)/M. However, the evidence suggests that size is the major cellulardeterminant of productivity; the apparent relationship betweencell cycle and productivity is secondary and can simply beascribed to the increasing size of cells as they progress thoughthe cell cycle. Thus, in addition to cell density and viabilitycell size is the cellular parameter which should be incorporatednot only into mathematical models of recombinant mammalian cellproduction processes but also into process monitoring andcontrol strategies.

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Authors: Lloyd, D. R., Holmes, P., Jackson, L. P., Emery, A. N., & Al-Rubeai, M.
Affiliations: University of Birmingham (GB)
ORCID: Lloyd, David R.
Venue: Cytotechnology
Publisher: Springer Science and Business Media LLC
Published: 2000-10
Volume: 34
Issue: 1-2
Pages: 59-70
ISSN: 0920-9069 (ISSN-L)
1573-0778
DOI: 10.1023/a:1008103730027
PMC: PMC3449736
OpenAlex: W1554602439
Cited by: 93
References: 31
Citations by year: 2025: 4 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 2 · 2016: 6 · 2015: 1 · 2014: 6 · 2013: 3 · 2012: 2
FWCI: 0.36
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Cytotechnology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Biotechnology and Biological Sciences Research Council
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: cell size, cell cycle, centrifugal elutriation, recombinant cell lines, G1 phase, S phase, G2/M phase, batch culture, process monitoring, process control

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Relationship between cell size, cell cycle and specific recombinant protein productivity

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