Document Detail


Hypoxia influences protein transport and epigenetic repression of CHO cell cultures in shake flasks.
MedLine Citation:
PMID:  25271019     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Shake flasks and bench-top bioreactors are widely used for cell culture process development, however, culture performances significantly differs between them. In order to apply the results received from small scale cultures to production scale, it is important to understand the mechanisms underlying the differences between different culture systems. This study analyzes the expression patterns of Chinese Hamster Ovary (CHO) cells producing IgG-fusion protein B0 cultured in shake flasks and 5-L bench-top bioreactors by CHO-specific DNA microarrays. The data show that hypoxia was present in shake flasks cultures but not in controlled, bench-top bioreactors. Hypoxic condition appeared to be associated with epigenetic repression resulting in decreased cell culture performance and protein productivity, which is also present during large-scale bioreactor operations due to oxygen gradients. High protein productivity was associated with increased cellular machineries for protein transport and secretion in conjunction with decreased epigenetic repression in bench-top bioreactor cultivation. Metal-ions could improve cell growth and protein production under hypoxia and this condition can be mimicked in small-scale bioreactors to facilitate cell culture process scale-up.
Authors:
Yueming Qian; Zizhuo Xing; Sherry Lee; Nancy A Mackin; Aiqing He; Paul S Kayne; Qin He; Nan-Xin Qian; Zheng Jian Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-1
Journal Detail:
Title:  Biotechnology journal     Volume:  -     ISSN:  1860-7314     ISO Abbreviation:  Biotechnol J     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-1     Completed Date:  -     Revised Date:  2014-10-2    
Medline Journal Info:
Nlm Unique ID:  101265833     Medline TA:  Biotechnol J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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