Optimizing Shear for Neural Stem Cell Differentiation

Abstract

Neural stem cells (NSC) have great potential for use in treatments for neurological disease by replacing damaged brain tissue via transplantation therapies. Growing NSC can be challenging, since the environment that the multipotent stem cells are grown in needs to be tightly controlled to ensure they differentiate into the desired stem cell line. Different methods have been considered to ensure the differentiation of these multipotent mesenchymal stem cells (MSC) into NSC, and finding the best design of bioreactor for growing any given stem cell line is an ongoing topic of inquiry in biomedical research.

The purpose of our project was to model a scalable suspension bioreactor in COMSOL Multiphysics that can be used to obtain a high enough yield of NSC for therapeutic applications. This was accomplished by providing the right shear environment for the NSC to differentiate in. We modeled fluid flow through the bioreactor using the Navier-Stokes equation, with Darcy flow through the filter near the middle of the bioreactor. We then adjusted the inlet volumetric flow rate to ensure that NSC are subjected to optimum shear rates during their residence time in the bioreactor. We performed a sensitivity analysis on our bioreactor and found that the shear distribution of the bioreactor is most sensitive to the density of the medium used to grow the cells.

In this report, we start by exploring some of the most current challenges faced when using different types of bioreactors to grow NSC, as well as some research that inspires our bioreactor design to be better than current options. A layout of our perfusion bioreactor is then detailed by a schematic, governing equation and boundary conditions before being modeled in COMSOL. Shear profiles are shown and discussed in the results section.

Fluid control has major implications for the internal environment of the bioreactor. We have shown that these aspects can be optimized to create a more suitable suspension environment for NSC incubation.