Dependence on glucose limitation of the pCO2 influences on CHO cell growth, metabolism and IgG production

• Published in: Biotechnology and bioengineering 2007-08, Vol.97 (6), p.1479-1488
• Main Authors: Takuma, Shinya, Hirashima, Chikashi, Piret, James M.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal - genetics; Biological and medical sciences; Biotechnology; carbon dioxide; Carbon Dioxide - metabolism; Cell Culture Techniques - methods; Cell Proliferation; CHO cell physiology; CHO Cells - physiology; Cricetinae; Cricetulus; Fundamental and applied biological sciences. Psychology; glucose; Glucose - metabolism; Humans; IgG galactosylation; Immunoglobulin G - genetics; Immunoglobulin G - metabolism; monoclonal antibody production; perfusion culture; Protein Engineering - methods; Transfection - methods
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.21376

The culture levels of glucose and CO2 have been reported to independently have important influences on mammalian cell processes. In this work the combined effects of glucose limitation and CO2 partial pressure (pCO2) on monoclonal antibody (IgG) producing Chinese Hamster Ovary cells were investigated in a perfusion reactor operated with controlled cell specific medium feed rate, pH and osmolality. Under high glucose conditions (14.3 ± 0.8 mM), the apparent growth rate decreased (from 0.021 to 0.009 h−1) as the pCO2 increased to ∼220 mmHg, while the cell specific IgG productivity was almost unchanged. The lactate yield from glucose was not affected by pCO2 up to ∼220 mmHg and glucose was mainly converted to lactate. A feed medium modification from high (33 mM) to low (6 mM) glucose resulted in