Dissecting cell death pathways in fed-batch bioreactors
David A Mentlak1, John Raven2, Tessa Moses3
1Department of Biology, University of York, Heslington, York, UK.
Biotechnology Journal
|December 1, 2023
Summary
Cell death in Chinese hamster ovary (CHO) cells impacts biologic production. This study reveals non-apoptotic cell death pathways, like parthanatos and ferroptosis, contribute to viability loss in industrial CHO cell cultures.
Area of Science:
- Biotechnology
- Cell Biology
- Biopharmaceutical Manufacturing
Background:
- Chinese hamster ovary (CHO) cells are critical for producing biologics, including monoclonal antibodies.
- Cell death in CHO cells significantly affects product yield and quality during biopharmaceutical manufacturing.
- Apoptosis was previously considered the primary cell death mechanism in CHO cells within bioreactors.
Purpose of the Study:
- To investigate the occurrence and mechanisms of cell death in an industrial antibody-producing CHO cell line under fed-batch culture conditions.
- To determine if non-apoptotic cell death pathways contribute to viability loss in CHO cells during biopharmaceutical production.
Main Methods:
- Analysis of cell viability in an industrial antibody-producing CHO cell line during fed-batch culture.
- Assessment of apoptosis markers (e.g., caspase activation) under standard and stressed conditions.
- Detection of markers for non-apoptotic cell death pathways, specifically parthanatos and ferroptosis.
Main Results:
- A decrease in CHO cell viability was observed towards the end of standard fed-batch cultures without significant apoptosis markers.
- Apoptosis was only induced under increased stress conditions, indicated by caspase activation.
- Markers for parthanatos and ferroptosis were detected during standard fed-batch culture, suggesting their involvement in viability loss.
Conclusions:
- Non-apoptotic cell death pathways, including parthanatos and ferroptosis, play a significant role in viability reduction in industrial CHO cell cultures.
- Targeting these non-conventional cell death mechanisms offers a potential strategy to enhance cell viability and improve biologic production in CHO cells.
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