The Numerical Estimation of Mass Transfer Coefficient of Oxygen in the Large-Scale Suspension Culture of iPS Cells

Abstract

In order to practically apply induced pluripotent stem (iPS) cells to regenerative medicine, a large amount of undifferentiated iPS cells should be produced by using an automated/scaled-up suspension culture system. However, in large-scale culture, oxygen supply to iPS cells away from the gas-liquid interface can be insufficient. In this numerical study, the oxygen supply performance is quantitatively evaluated by estimating the volumetric mass transfer coefficient of oxygen in the suspension culture of iPS cells. And, focusing on shaking culture, where shear stress that causes death or differentiation of iPS cells is relatively reduced, we compare two different shaking methods: one direction rotation (ODR) and periodic alternate rotation (PAR). The validity of the volumetric mass transfer coefficient calculation is confirmed by comparison with the experiment. The PAR method is superior to the ODR method in terms of oxygen supply because of higher turbulence intensities, but it is much less energy efficient than the ODR method. In the ODR method, the cell size is thought to be non-uniform since iPS cells are aggregated due to cell sedimentation. On the other hand, in the PAR method, cell sedimentation is suppressed by controlling the Froude number (Fr).