Simulation of mammalian cell population dynamics

Abstract

Applied is a systems view to modelling of mammalian cell cultivation in a bioreactor for biotechnological applications. Proposed is a model with a hierarchical structure with three levels: the macroscopic level of a reactor, microscopic level of a cell population, and molecular level of protein interactions with cyclin dependent kineases. The macroscopic model provides basis for production process control by optimal feeding of nutrients and growth factors during cultivation. The microscopic model simplifies a cell population into three pools of cells: P proliferating, Q quiescent, and D dead cells. Dynamics of cell population is determined by the least square estimation of the specific rates of the pool transitions. The molecular model enables theoretical basis for prediction of G1/S transition and the rate of transition from proliferating cells into quiescent state. Conceptual application of the molecular model in conjunction with the mammalian cell production system is discussed