中国仓鼠卵巢细胞
程序性细胞死亡
细胞凋亡
细胞生物学
活力测定
细胞培养
生物
坏死性下垂
生物制药
单克隆抗体
细胞生长
抗体
生物化学
免疫学
生物技术
遗传学
作者
David A. Mentlak,John A. Raven,Tessa Moses,Fraser Massie,Nicholas Barber,Robyn Hoare,Graham J. Burton,Ahn Na Young,Leon P. Pybus,Susan J. Rosser,Robert J. White,Dániel Ungár,Nia J. Bryant
标识
DOI:10.1002/biot.202300257
摘要
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.
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