5 years ago

Kinetic modeling of mammalian cell culture bioprocessing: the quest to advance biomanufacturing

Kok Siong Ang, Meiyappan Lakshmanan, Dong-Yup Lee, Seongkyu Yoon, Rudiyanto Gunawan, Zhuangrong Huang, Sarantos Kyriakopoulos
Kinetic modeling is the most suitable framework to describe the dynamic behavior of mammalian cell culture although its industrial application is still in its infancy. Herein, we review mammalian bioprocess relevant kinetic models and found that the simple unstructured-unsegregated approach utilizing empirical Monod type kinetics based on limiting substrates and inhibitory metabolites is commonly used due to the traceability and simple formalism. Notably, the available kinetic models are typically small to moderate in size and the development of large-scale models is severely hampered by the scarcity of kinetic data and limitations in current parameter estimation methods. The recent availability of abundant high-throughput multi-omics datasets from mammalian cell culture have now paved ways to improve parameterization of kinetic models, and integrate regulatory, signaling, and product quality related intracellular events, as well as cellular metabolism within the modeling framework. Ultimately, we foresee that multi-scale modeling is the way forward in building predictive kinetic models of mammalian cell culture to advance biomaufacturing.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/biot.201700229

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