Abstract

Chinese hamster ovary (CHO) cells have been the most commonly used mammalian host for large-scale commercial production of therapeutic proteins, such as monoclonal antibodies. Enhancement of productivity of these CHO cells is one of the top priorities in the biopharmaceutical industry to reduce manufacturing cost. Although there are many different methods (e.g. temperature, pH, feed) to improve protein production in CHO cells, the role of physiologically relevant hydrostatic pressure in CHO cell culture has not been reported yet. In this study, four different hydrostatic pressures (0, 30, 60, and 90 mmHg) were applied to batch CHO cells, and their cell growth/metabolism and IgG1 production were examined. Our results indicate that hydrostatic pressure can increase the maximum cell concentration by up to 50%. Moreover, overall IgG1 concentration on Day 5 showed that 30 mmHg pressure can increase IgG1 production by 26%. The percentage of non-disulphide-linked antibody aggregates had no significant change under pressure. Besides, no significant difference was observed between 30 mmHg and no pressure conditions in terms of cell clumping formation. All these findings are important for the optimization of fed-batch or perfusion culture for directing cell growth and improving antibody production.

Details

Title
Investigating the influence of physiologically relevant hydrostatic pressure on CHO cell batch culture
Author
Shang Menglin 1 ; Kwon Taehong 2 ; Hamel, Jean-Francois P 3 ; Lim, Chwee Teck 4 ; Khoo Bee Luan 5 ; Han Jongyoon 6 

 Singapore-MIT Alliance for Research and Technology (SMART) Centre, Critical Analytics for Manufacturing Personalized-Medicine (CAMP) IRG, Singapore, Singapore (GRID:grid.429485.6) (ISNI:0000 0004 0442 4521); National University of Singapore, Department of Biomedical Engineering, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431) 
 Massachusetts Institute of Technology, Research Laboratory of Electronics, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786) 
 Massachusetts Institute of Technology, Department of Chemical Engineering, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786) 
 Singapore-MIT Alliance for Research and Technology (SMART) Centre, Critical Analytics for Manufacturing Personalized-Medicine (CAMP) IRG, Singapore, Singapore (GRID:grid.429485.6) (ISNI:0000 0004 0442 4521); National University of Singapore, Mechanobiology Institute, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); National University of Singapore, Department of Biomedical Engineering, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); National University of Singapore, Department of Mechanical Engineering, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); Institute for Health Innovation and Technology, Singapore, Singapore (GRID:grid.4280.e) 
 City University of Hong Kong, Department of Biomedical Engineering, Kowloon Tong, Hong Kong (GRID:grid.35030.35) (ISNI:0000 0004 1792 6846) 
 Singapore-MIT Alliance for Research and Technology (SMART) Centre, Critical Analytics for Manufacturing Personalized-Medicine (CAMP) IRG, Singapore, Singapore (GRID:grid.429485.6) (ISNI:0000 0004 0442 4521); National University of Singapore, Department of Mechanical Engineering, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, Department of Biological Engineering, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786); Massachusetts Institute of Technology, Research Laboratory of Electronics, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2476255043
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.