Computations of flow environments in medium-scale stirred-tank bioreactors for stem cell expansion

The flow in a New Brunswick Scientific (NBS (now Eppendorf)) 5 L stirred-tank bioreactor (STR) partially filled with 2.2 L of water and agitated at 60 rpm using a pitched-blade impeller is studied in this work, to determine the suitability of the configuration for expanding stem cell lines. Computational Fluid Dynamics (CFD) model development and testing in this work has found Large Eddy Simulation (LES) to be essential for model fidelity and for capturing spatiotemporal stress fluctuations. Stresses were at levels similar to or even higher than those known to damage stem cells or modulate their cellular function to favour differentiation instead of phenotype maintenance. The results raise questions as to the appropriateness of such STRs for stem cell expansion, and motivate better experimental studies to properly quantify the spatiotemporal variability in fluid shear stresses and its effect on stem cell expansion and stem cell fate.