Monoclonal antibody productivity and the metabolic pattern of perfusion cultures under varying oxygen tensions

The metabolic pattern and cell culture kinetics of high‐cell‐density perfusion cultures were compared under two different oxygen transfer conditions: oxygen limiting and not limiting. When oxygen was a limiting factor during perfusion culture, both specific glucose uptake and lactate production rate...

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Bibliographic Details
Published in:Biotechnology and bioengineering 1993-08, Vol.42 (4), p.430-439
Main Authors: Shi, Yuan, Ryu, Dewey D. Y., Park, Sun Ho
Format: Article
Language:English
Subjects:
Animal cells
Biological and medical sciences
Biotechnology
Eukaryotic cell cultures
Fundamental and applied biological sciences. Psychology
high-cell-density perfusion cultivation
hydrodynamic shear
MAb productivity
metabolic pattern
Methods. Procedures. Technologies
Miscellaneous
oxygen effect
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Summary:The metabolic pattern and cell culture kinetics of high‐cell‐density perfusion cultures were compared under two different oxygen transfer conditions: oxygen limiting and not limiting. When oxygen was a limiting factor during perfusion culture, both specific glucose uptake and lactate production rates increased, compared to non‐oxygen‐limited condition, by about 60% and 30%, respectively. The specific glutamine uptake rate under oxygen‐limited conditions was almost 4.0 times higher than that under non‐oxygen‐limited conditions. The activity of lactate dehydrogenase (LDH) released into the medium by the dead cells can be used as an indicator for the metabolic and physiological conditions related to oxygen limitation. There was a 3.2 times higher specific rate of LDH activity released by dead cells in oxygen‐limited cultures than those in non‐oxygen‐limited cultures. The specific production rate of monoclonal antibody was not significantly affected by the oxygen transfer conditions during the rapid cell growth period, but it rapidly increased toward the end of perfusion cultures. The higher perfusion rate may have limited further cell growth during high‐cell‐density perfusion culture, because cell damage was caused by the hydrodynamic shear within a hollow fiber microfiltration cartridge installed to withdraw the spent medium and the waste metabolites. © 1993 John Wiley & Sons, Inc.
ISSN:0006-3592
1097-0290
DOI:10.1002/bit.260420405