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Metabolic analysis of antibody producing Chinese hamster ovary cell culture under different stresses conditions

Paper ID Volume ID Publish Year Pages File Format Full-Text
19989 43151 2016 8 PDF Available
Title
Metabolic analysis of antibody producing Chinese hamster ovary cell culture under different stresses conditions
Abstract

•Addition of trehalose or NaCl suppressed cell growth, but enhanced antibody production.•The dynamics of extra- and intracellular metabolome was closely related to biological functions.•Reporter metabolites are identified whose concentrations greatly change between the NaCl and trehalose cultures.•Critical metabolites that directly relate to cellular phenotypes are identified in the NaCl and trehalose cultures.•Antibody production mechanisms are suggested to be complicated.

Chinese hamster ovary (CHO) cells are commonly used as the host cell lines concerning their ability to produce therapeutic proteins with complex post-translational modifications. In this study, we have investigated the time course extra- and intracellular metabolome data of the CHO–K1 cell line, under a control and stress conditions. The addition of NaCl and trehalose greatly suppressed cell growth, where the maximum viable cell density of NaCl and trehalose cultures were 2.2-fold and 2.8-fold less than that of a control culture. Contrariwise, the antibody production of both the NaCl and trehalose cultures was sustained for a longer time to surpass that of the control culture. The NaCl and trehalose cultures showed relatively similar dynamics of cell growth, antibody production, and substrate/product concentrations, while they indicated different dynamics from the control culture. The principal component analysis of extra- and intracellular metabolome dynamics indicated that their dynamic behaviors were consistent with biological functions. The qualitative pattern matching classification and hierarchical clustering analyses for the intracellular metabolome identified the metabolite clusters whose dynamic behaviors depend on NaCl and trehalose. The volcano plot revealed several reporter metabolites whose dynamics greatly change between in the NaCl and trehalose cultures. The elastic net identified some critical, intracellular metabolites that are distinct between the NaCl and trehalose. While a relatively small number of intracellular metabolites related to the cell growth, glucose, glutamine, lactate and ammonium ion concentrations, the mechanism of antibody production was suggested to be very complicated or not to be explained by elastic net regression analysis.

Keywords
Metabolomics; Biotechnology; Chinese hamster ovary cells; NaCl and trehalose culture; Cell growth; Antibody production; Statistical analysis
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Metabolic analysis of antibody producing Chinese hamster ovary cell culture under different stresses conditions
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Bioscience and Bioengineering - Volume 122, Issue 1, July 2016, Pages 117–124
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us