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BMC Biotechnology

, 14:72

Cellular and tissue engineering

Abstract

BackgroundIn 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.

ResultsTo 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.

ConclusionsA 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.

KeywordsAvian cell line AGE1.CR.pIX Biomass composition Flux variability analysis Metabolic network modeling Glutaminolysis Electronic supplementary materialThe online version of this article doi:10.1186-1472-6750-14-72 contains supplementary material, which is available to authorized users.

Verena Lohr, Oliver Hädicke contributed equally to this work.

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Autor: Verena Lohr - Oliver Hädicke - Yvonne Genzel - Ingo Jordan - Heino Büntemeyer - Steffen Klamt - Udo Reichl

Fuente: https://link.springer.com/







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