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Open Access Research article

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

Verena Lohr12*, Oliver Hädicke1, Yvonne Genzel1, Ingo Jordan2, Heino Büntemeyer3, Steffen Klamt1 and Udo Reichl14

Author Affiliations

1 Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106 Magdeburg, Germany

2 Current address: ProBioGen AG, Goethestr. 54, 13086 Berlin, Germany

3 Cell Culture Technology, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany

4 Bioprocess Engineering, Otto von Guericke University Magdeburg, Universitätsplatz 2, 39106 Magdeburg, Germany

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BMC Biotechnology 2014, 14:72  doi:10.1186/1472-6750-14-72

Published: 30 July 2014

Abstract

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.

Keywords:
Avian cell line AGE1.CR.pIX; Biomass composition; Flux variability analysis; Metabolic network modeling; Glutaminolysis