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The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis

BACKGROUND: In human vaccine manufacturing some pathogens such as Modified Vaccinia Virus Ankara, measles, mumps virus as well as influenza viruses are still produced on primary material derived from embryonated chicken eggs. Processes depending on primary cell culture, however, are difficult to ada...

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Autores principales: Lohr, Verena, Hädicke, Oliver, Genzel, Yvonne, Jordan, Ingo, Büntemeyer, Heino, Klamt, Steffen, Reichl, Udo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124504/
https://www.ncbi.nlm.nih.gov/pubmed/25077436
http://dx.doi.org/10.1186/1472-6750-14-72
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author Lohr, Verena
Hädicke, Oliver
Genzel, Yvonne
Jordan, Ingo
Büntemeyer, Heino
Klamt, Steffen
Reichl, Udo
author_facet Lohr, Verena
Hädicke, Oliver
Genzel, Yvonne
Jordan, Ingo
Büntemeyer, Heino
Klamt, Steffen
Reichl, Udo
author_sort Lohr, Verena
collection PubMed
description BACKGROUND: In human vaccine manufacturing some pathogens such as Modified Vaccinia Virus Ankara, measles, mumps virus as well as influenza viruses are still produced on primary material derived from embryonated chicken eggs. Processes depending on primary cell culture, however, are difficult to adapt to modern vaccine production. Therefore, we derived previously a continuous suspension cell line, AGE1.CR.pIX, from muscovy duck and established chemically-defined media for virus propagation. RESULTS: To better understand vaccine production processes, we developed a stoichiometric model of the central metabolism of AGE1.CR.pIX cells and applied flux variability and metabolic flux analysis. Results were compared to literature dealing with mammalian and insect cell culture metabolism focusing on the question whether cultured avian cells differ in metabolism. Qualitatively, the observed flux distribution of this avian cell line was similar to distributions found for mammalian cell lines (e.g. CHO, MDCK cells). In particular, glucose was catabolized inefficiently and glycolysis and TCA cycle seem to be only weakly connected. CONCLUSIONS: A distinguishing feature of the avian cell line is that glutaminolysis plays only a minor role in energy generation and production of precursors, resulting in low extracellular ammonia concentrations. This metabolic flux study is the first for a continuous avian cell line. It provides a basis for further metabolic analyses to exploit the biotechnological potential of avian and vertebrate cell lines and to develop specific optimized cell culture processes, e.g. vaccine production processes.
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spelling pubmed-41245042014-08-12 The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis Lohr, Verena Hädicke, Oliver Genzel, Yvonne Jordan, Ingo Büntemeyer, Heino Klamt, Steffen Reichl, Udo BMC Biotechnol Research Article BACKGROUND: In human vaccine manufacturing some pathogens such as Modified Vaccinia Virus Ankara, measles, mumps virus as well as influenza viruses are still produced on primary material derived from embryonated chicken eggs. Processes depending on primary cell culture, however, are difficult to adapt to modern vaccine production. Therefore, we derived previously a continuous suspension cell line, AGE1.CR.pIX, from muscovy duck and established chemically-defined media for virus propagation. RESULTS: To better understand vaccine production processes, we developed a stoichiometric model of the central metabolism of AGE1.CR.pIX cells and applied flux variability and metabolic flux analysis. Results were compared to literature dealing with mammalian and insect cell culture metabolism focusing on the question whether cultured avian cells differ in metabolism. Qualitatively, the observed flux distribution of this avian cell line was similar to distributions found for mammalian cell lines (e.g. CHO, MDCK cells). In particular, glucose was catabolized inefficiently and glycolysis and TCA cycle seem to be only weakly connected. CONCLUSIONS: A distinguishing feature of the avian cell line is that glutaminolysis plays only a minor role in energy generation and production of precursors, resulting in low extracellular ammonia concentrations. This metabolic flux study is the first for a continuous avian cell line. It provides a basis for further metabolic analyses to exploit the biotechnological potential of avian and vertebrate cell lines and to develop specific optimized cell culture processes, e.g. vaccine production processes. BioMed Central 2014-07-30 /pmc/articles/PMC4124504/ /pubmed/25077436 http://dx.doi.org/10.1186/1472-6750-14-72 Text en Copyright © 2014 Lohr et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Lohr, Verena
Hädicke, Oliver
Genzel, Yvonne
Jordan, Ingo
Büntemeyer, Heino
Klamt, Steffen
Reichl, Udo
The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis
title The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis
title_full The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis
title_fullStr The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis
title_full_unstemmed The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis
title_short The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis
title_sort avian cell line age1.cr.pix characterized by metabolic flux analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124504/
https://www.ncbi.nlm.nih.gov/pubmed/25077436
http://dx.doi.org/10.1186/1472-6750-14-72
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