Hydrodynamics in Stirred Suspension Bioreactors from CFD Models for Expansion of Induced Pluripotent Stem Cells

Induced pluripotent stem cells (iPSCs) have the ability to proliferate in culture and can differentiate into many other tissue types and as they can be derived from somatic cells, their use would overcome existing ethical issues associated with embryonic stem cells in future stem cell-based applications.  Most of the current iPSC research focuses on improving the safety and efficiency of reprograming somatic cells to iPSCs. However, for iPSCs to be used in clinical applications, establishing a robust cell manufacturing process is an essential step. The challenge of cell manufacturing is to produce large quantities of cells while maintaining the desired phenotype. Stirred suspension bioreactors have been used by our group and many others for the expansion of a range of stem cell types. This culture system provides a well-mixed environment and for aggregate-forming cells, such as human iPSCs, the culture environment is able to control the size of the aggregates formed – thus generating more standardized cell populations. We have previously shown that shear stress in stirred suspension bioreactors plays an important role in stem cell proliferation and differentiation due to possible mechanotransduction mechanisms. Understanding the hydrodynamic environment and in particular the shear stress distribution inside stirred suspension bioreactors is a fundamental step to develop cell manufacturing processes. Here, we used computational fluid dynamics (CFD) to understand the flow regime and shear stress distribution at different agitation rates, viscosities, and geometries of vessel and impeller. The shear stress-cell growth relationship and shear stress-cell aggregate distribution was also examined by comparing our model to established experimental data. These key relationships provide the basis for designing robust cell manufacturing processes that meet specific clinical applications.