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High Cell Density Perfusion Culture has a Maintained Exoproteome and Metabolome
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
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Number of Authors: 132018 (English)In: Biotechnology Journal, ISSN 1860-6768, E-ISSN 1860-7314, Vol. 13, no 10, article id 1800036Article in journal (Refereed) Published
Abstract [en]

The optimization of bioprocesses for biopharmaceutical manufacturing by Chinese hamster ovary (CHO) cells can be a challenging endeavor and, today, heavily relies on empirical methods treating the bioreactor process and the cells as black boxes. Multi-omics approaches have the potential to reveal otherwise unknown characteristics of these systems and identify culture parameters to more rationally optimize the cultivation process. Here, the authors have applied both metabolomic and proteomic profiling to a perfusion process, using CHO cells for antibody production, to explore how cell biology and reactor environment change as the cell density reaches 200x10(6)cellsmL(-1). The extracellular metabolic composition obtained in perfusion mode shows a markedly more stable profile in comparison to fed-batch, despite a far larger range of viable cell densities in perfusion. This stable profile is confirmed in the extracellular proteosome. Furthermore, the proteomics data shows an increase of structural proteins as cell density increases, which could be due to a higher shear stress and explain the decrease in cell diameter at very high cell densities. Both proteomic and metabolic results shows signs of oxidative stress and changes in glutathione metabolism at very high cell densities. The authors suggest the methodology presented herein to be a powerful tool for optimizing processes of recombinant protein production.

Place, publisher, year, edition, pages
2018. Vol. 13, no 10, article id 1800036
Keywords [en]
bioreactor, CHO cells, industrial biotechnology, metabolomics, proteomics
National Category
Biological Sciences Environmental Biotechnology
Identifiers
URN: urn:nbn:se:su:diva-161007DOI: 10.1002/biot.201800036ISI: 000446009100009PubMedID: 29957873OAI: oai:DiVA.org:su-161007DiVA, id: diva2:1255961
Available from: 2018-10-15 Created: 2018-10-15 Last updated: 2018-10-15Bibliographically approved

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Åberg, MagnusChotteau, Veronique
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