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Development of a Scale-Down Model of hydrodynamic stress to study the performance of an industrial CHO cell line under simulated production scale bioreactor conditions

Paper ID Volume ID Publish Year Pages File Format Full-Text
23559 43452 2013 9 PDF Available
Title
Development of a Scale-Down Model of hydrodynamic stress to study the performance of an industrial CHO cell line under simulated production scale bioreactor conditions
Abstract

The objective of this study was to develop a Scale-Down Model of a hydrodynamic stress present in large scale production bioreactors to investigate the performance of CHO cells under simulated production bioreactor conditions. Various levels of hydrodynamic stress were generated in 2 L bioreactors mimicking those present in different locations of a large scale stirred tank bioreactor.In general, it was observed that tested cells are highly robust against the effect of hydrodynamic stress. However, at elevated hydrodynamic stress equivalent to an average energy dissipation rate, 〈ε〉ε, equal to 0.4 W/kg, the specific monoclonal antibody productivity, qmAbqmAb, decreased by 25% compared to the cultivation conditions corresponding to 〈ε〉ε equal to 0.01 W/kg. Even stronger decrease of qmAbqmAb, in the order of 30%, was observed when 〈ε〉ε was periodically oscillating between 0.01 and 0.4 W/kg to simulate the repeated passage of cells through the highly turbulent impeller discharge zone of a production scale bioreactor. Despite this effect, no changes in metabolite consumption or byproduct formation were observed. Furthermore, considering the experimental error product quality was independent of the applied 〈ε〉ε. To achieve a molecular insight into the observed drop of cellular productivity, a transcriptome analysis using mRNA microarrays was performed. It was found that transcripts related to DNA damage and repair mechanisms were upregulated when high 〈ε〉ε was applied for cultivation.

► We developed a Scale-Down Model of hydrodynamic stress in large scale bioreactors. ► At high and oscillating hydrodynamic stress, specific productivity was reduced. ► Metabolite consumption, byproduct formation or product quality were not affected. ► DNA damage and repair mechanisms were upregulated under elevated stress conditions.

Keywords
ANOVA, analysis of variance; bG0, nongalactosylated glycan structure; bG1, monogalactosylated glycan structure; bG2, bigalactosylated glycan structure; HighM, high-mannose isoforms; CHO, Chinese Hamster Ovary; VCD, viable cell density [cells/mL]Scale-Down
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Development of a Scale-Down Model of hydrodynamic stress to study the performance of an industrial CHO cell line under simulated production scale bioreactor conditions
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 164, Issue 1, 10 March 2013, Pages 41–49
Authors
, , , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us