Metabolic flux and nutrient uptake modeling of normal and apoptotic CHO cells

Applying metabolic flux analysis as the basis, a dynamic mathematical model was developed for describing the growth and metabolic behavior of CHO cells producing monoclonal antibodies (MAb) in batch culture. The viable cell population was assumed to consist of normal growing, normal non-growing and apoptotic cell subpopulations. A logistic cell growth model was derived that differentiates between actively dividing, resting, and apoptotic cells. The rate of apoptotic cell formation was assumed to have a second order dependence on the normal cell concentration. The proposed mathematical model for metabolites included distinct terms that reflected the metabolic rates of growing and non-growing cell populations. The results of the prediction were in good agreement with experimental data for different initial conditions.