Macroscopic modeling of mammalian cell growth and metabolism

Abstract

We review major modeling strategies and methods to understand and simulate the macroscopic behavior of mammalian cells. These strategies comprise two important steps: the first step is to identify stoichiometric relationships for the cultured cells connecting the extracellular inputs and outputs. In a second step, macroscopic kinetic models are introduced. These relationships together with bioreactor and metabolite balances provide a complete description of a system in the form of a set of differential equations. These can be used for the simulation of cell culture performance and further for optimization of production.

Workflow for Target‐Oriented Parametrization of an Enhanced Mechanistic Cell Culture Model

“…One reason is that several mechanisms (e.g., lactate consumption) are clone dependent. Therefore several models describing mammalian cell cultures exist, for extensive reviews and collections see e.g . Additionally, macroscopic models typically ignore factors like pH, pCO 2 , or osmolality despite their effect, e.g., on the growth of CHO cells .…”

Between the Poles of Data‐Driven and Mechanistic Modeling for Process Operation

“…Mechanistic models (M‐models) are generally preferred when the model is used over a wide range of operating conditions. They can deliver good results even for situations that were never observed before as long as the relevant phenomena are considered adequately in the models , . This becomes important if a chemical plant gets into an undesired state, e.g., during start‐up phase or when new grades are to be produced.…”

Current state and perspectives in modeling and control of human pluripotent stem cell expansion processes in stirred‐tank bioreactors

“…C oxy /( K oxy + C oxy ) and C glc /( K glc + C glc ) are the Monod terms; C oxy and C glc are variables representing the concentrations of dissolved oxygen and glucose, respectively, and K oxy and K glc are constants. With some modification, Monod kinetics are capable of simulating various phenomena observed during cell expansion processes, such as saturation, inhibition and limitation by substrates and other environmental components . From the viewpoint of engineering controls, development of simple kinetic models may provide a good perspective for model‐based improvement of hPSC expansion processes, as identification of kinetic models may be performed using only a limited amount of experimental data.…”