Mentlak, David A, Raven, John, Moses, Tessa et al. (10 more authors) (2024) Dissecting cell death pathways in fed-batch bioreactors. Biotechnology journal. 2300257. ISSN 1860-7314
Abstract
Chinese hamster ovary (CHO) cells are widely used for production of biologics including therapeutic monoclonal antibodies. Cell death in CHO cells is a significant factor in biopharmaceutical production, impacting both product yield and quality. Apoptosis has previously been described as the major form of cell death occurring in CHO cells in bioreactors. However, these studies were undertaken when less was known about non-apoptotic cell death pathways. Here, we report the occurrence of non-apoptotic cell death in an industrial antibody-producing CHO cell line during fed-batch culture. Under standard conditions, crucial markers of apoptosis were not observed despite a decrease in viability towards the end of the culture; only by increasing stress within the system did we observe caspase activation indicative of apoptosis. In contrast, markers of parthanatos and ferroptosis were observed during standard fed-batch culture, indicating that these non-apoptotic cell death pathways contribute to viability loss under these conditions. These findings pave the way for targeting non-conventional cell death pathways to improve viability and biologic production in CHO cells.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The Authors. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 17 Jan 2024 11:50 |
Last Modified: | 04 Feb 2025 00:09 |
Published Version: | https://doi.org/10.1002/biot.202300257 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1002/biot.202300257 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:207818 |
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