Growth and death kinetics of CHO cells cultivated in continuous bioreactor at various agitation rates

Abstract

Mammalian cells are known to be sensitive to hydrodynamic stresses. Therefore, soft agitation and aeration are generally recommended in culture bioreactor to prevent cell damages. Nevertheless, at the industrial scale, this may induce CO2 accumulation, high mixing times, poor air dispersion and concentration gradients. In batch reactor, we have previously found that growth kinetics of CHO cells could be enhanced by increasing stirring frequencies from 80 to 600 rpm. However, these studies were limited in time due to depletion of substrates leading to a cell death which is not associated to hydrodynamic constraints. To overcome the effects on cell death from those nutritional limitations, in this work, longer stationary cultures of CHO cells were carried out in continuous mode in a 2-liter reactor operating with various stirring profiles.