Amino acid degradation pathway inhibitory by-products trigger apoptosis in CHO cells.
CHO cells
cell death
high cell density culture
inhibitory by-products
proteomics
Journal
Biotechnology journal
ISSN: 1860-7314
Titre abrégé: Biotechnol J
Pays: Germany
ID NLM: 101265833
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
revised:
25
11
2023
received:
12
07
2023
accepted:
13
12
2023
medline:
20
2
2024
pubmed:
20
2
2024
entrez:
20
2
2024
Statut:
ppublish
Résumé
Chinese hamster ovary (CHO) cells are widely used to produce complex biopharmaceuticals. Improving their productivity is necessary to fulfill the growing demand for such products. One way to enhance productivity is by cultivating cells at high densities, but inhibitory by-products, such as metabolite derivatives from amino acid degradation, can hinder achieving high cell densities. This research examines the impact of these inhibitory by-products on high-density cultures. We cultured X1 and X2 CHO cell lines in a small-scale semi-perfusion system and introduced a mix of inhibitory by-products on day 10. The X1 and X2 cell lines were chosen for their varied responses to the by-products; X2 was susceptible, while X1 survived. Proteomics revealed that the X2 cell line presented changes in the proteins linked to apoptosis regulation, cell building block synthesis, cell growth, DNA repair, and energy metabolism. We later used the AB cell line, an apoptosis-resistant cell line, to validate the results. AB behaved similar to X1 under stress. We confirmed the activation of apoptosis in X2 using a caspase assay. This research provides insights into the mechanisms of cell death triggered by inhibitory by-products and can guide the optimization of CHO cell culture for biopharmaceutical manufacturing.
Identifiants
pubmed: 38375561
doi: 10.1002/biot.202300338
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2300338Subventions
Organisme : Therapeutic Innovation Australia
Organisme : TIA through the National Collaborative Research Infrastructure Strategy
Organisme : Queensland Metabolomics and Proteomics
Organisme : Australian Research Council Training Centre
Organisme : Biopharmaceutical Innovation
ID : IC160100027
Organisme : Advance Queensland Women's Research Assistance Program
ID : WRAP213-2019RD1
Organisme : Advance Queensland Industry Research Fellowship
ID : AQIRF036-2022RD5
Organisme : Australian Research Council Centre of Excellence in Synthetic Biology
ID : CE200100029
Informations de copyright
© 2024 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.
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