Aggregate Perfusion Medium Exchange in Vertical-Wheel® Bioreactors for Scalable PSC Production

This white paper examines medium exchange strategies for scaling pluripotent stem cell (PSC) aggregate expansion in PBS Vertical-Wheel® Bioreactors. It explains how conventional settled medium exchange interrupts agitation and allows aggregates to merge, increasing size heterogeneity that can affect cell quality and downstream differentiation. The paper compares settled medium exchange with a filter-based perfusion approach characterized in PBS-0.5 Mini vessels. Perfusion maintained agitation during medium exchange and produced consistent growth and metabolic rates, with smaller, more spherical, and more homogeneous aggregates than settled controls. Scale-up into the PBS-3 bioreactor showed consistent growth kinetics, metabolite profiles, and aggregate morphology across scales. The findings support perfusion medium exchange as a scalable method for maintaining PSC aggregate homogeneity during larger-scale production.