Analyzing the Differentiation of Pluripotent Stem Cells in 3D Environments via Rules-Based Computational Modeling

Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into cell types of all germ lineages, making them a potentially robust cell source for regenerative medicine therapies and cell-based diagnostics. The difficulty in controlling and predicting the fate and behavior of ESCs currently limits their potential uses in medicine and biotechnology. A common approach to inducing the differentiation of ESCs is to create multi-cellular aggregates referred to as embryoid bodies (EBs); however, this approach currently fails to provide the degree of control and reproducibility necessary for regenerative medicine and stem cell bio-manufacturing applications. The goal of this project is to develop a computational model which can predict phenotypic changes during ESC differentiation within 3-dimensional EBs. Cells within the EB are modeled as spheres using two rules. First, cells can’t take up the same space as another cell. Second cells are not deformable. By allowing cells to interact with their environment via these simple rules EB structural parameters were accurately predicted. Correctly modeling the EB starting structure is essential as this model will be used as a scaffold on which to add more complex rules. Future work will involve further characterization of the starting EB structure, implementation of a particle based diffusion model, and eventually application of a simple differentiation model.