A macrokinetic and regulator model for myeloma cell culture based on metabolic balance of pathways

Abstract

A macrokinetic model is proposed to simulate the growth and metabolism of myeloma cell line in batch and fed-batch cultures. The model describes glycolysis, glutaminolysis, the TCA cycle, respiratory chain, formation of metabolites, as well as cell growth and death. In particular, metabolic shift in the glucose utilization is considered in response to the change of glycolysis rate during the cultivation. A closed loop regulator is introduced to approximate the induction of enzyme pool during lag phase after inoculation. Based on the model, the specific consumption rate of substrate, the specific growth rate, the specific acetyl CoA formation rate as well as the specific oxygen uptake rate are estimated. The specific substrate consumption rate and the specific growth rate are then coupled into a bioreactor model, which delivers the key variables, i.e., cell density, substrate and metabolite concentrations. Batch and fed-batch cultivations were used to validate the model.