Document Detail


Process parameter shifting: Part I. Effect of DOT, pH, and temperature on the performance of Epo-Fc expressing CHO cells cultivated in controlled batch bioreactors.
MedLine Citation:
PMID:  16736530     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The impact of process environment changes on process performance is one of the most crucial process safety issues when cultivating mammalian cells in a bioreactor. In contrast, directed shifting of process parameters can also be used as an optimization tool providing higher cell and product yields. Compared to other strategies that also aim on the regulation of cell growth and protein expression process parameter shifts can be easily performed without reagent addition or even genetic modification of the host cell line. However, a successful application of changing process conditions implies a profound understanding of the provoked physiological changes within the cells. In a systematic approach we varied the dissolved oxygen tension (DOT), pH, and temperature of CHO cultures in controlled bioreactors and investigated the impact on growth, productivity, metabolism, product quality and cell cycle distribution using a recombinant CHO cell line expressing the highly glycosylated fusion protein Epo-Fc. We found the reduction of cultivation temperature and the reduction of (external) pH to exert the most significant effects on process performance by mainly reducing cell growth and metabolism. With respect to the cell line used we identified a set of parameters capable of affecting cell proliferation in favor of an increased specific productivity and total product yield. The well directed alteration of the process environment has emerged as a tool adequate for further process optimization applying a biphasic cultivation strategy.
Authors:
Evelyn Trummer; Katharina Fauland; Silke Seidinger; Kornelia Schriebl; Christine Lattenmayer; Renate Kunert; Karola Vorauer-Uhl; Robert Weik; Nicole Borth; Hermann Katinger; Dethardt Müller
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biotechnology and bioengineering     Volume:  94     ISSN:  0006-3592     ISO Abbreviation:  Biotechnol. Bioeng.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-25     Completed Date:  2006-09-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7502021     Medline TA:  Biotechnol Bioeng     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1033-44     Citation Subset:  IM    
Copyright Information:
Copyright 2006 Wiley Periodicals, Inc.
Affiliation:
Department of Biotechnology, Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences Vienna, Muthgasse 18, 1190 Vienna, Austria.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bioreactors / microbiology*
CHO Cells / cytology,  physiology*
Cell Culture Techniques / methods*
Computer Simulation
Cricetinae
Cricetulus
Erythropoietin / genetics,  metabolism*
Humans
Hydrogen-Ion Concentration
Immunoglobulin Fc Fragments / genetics,  metabolism
Immunoglobulin G / genetics,  metabolism*
Models, Biological*
Oxygen / metabolism*
Oxygen Consumption / physiology
Protein Engineering / methods
Recombinant Fusion Proteins / biosynthesis
Temperature
Chemical
Reg. No./Substance:
0/Immunoglobulin Fc Fragments; 0/Immunoglobulin G; 0/Recombinant Fusion Proteins; 11096-26-7/Erythropoietin; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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