Embryonic stem cells (ESC) are generating significant interest due to their ability to expand in culture and differentiate into a variety of cell types including hepatocytes, pancreatic beta cells, osteoblasts, cardiomyocytes, endothelial cells and neural cells.  These cells may provide a potential source of cells for numerous diseases including diabetes and liver failure.  One of the main challenges preventing ES cell based therapies reaching their full potential is the lack methods to homogeneously direct ESC differentiation. Currently, various microscale technologies have been adopted in the tissue engineering field in order to specifically control the spatial and temporal features of the cellular microenvironment. We have recently developed a stem cell culture platform using a microwell array. This platform demonstrated an ability to precisely control the size and shape of the embryoid bodies (EBs). We observed that the differentiation of EBs was regulated in a size-dependent manner. Specifically, the larger EBs had a preference to differentiation into cardiac cells, whereas endothelial cell differentiation was enhanced in smaller EBs.  Additionally, we combined microfabrication techniques with photodefinable hydrogels and encapsulated cells inside microscale hydrogel blocks generating 3D tissue architectures in a spatially controlled manner. By using this approach, we demonstrated a platform where individual EBs could be exposed to different environments such as a gelatin-based matrix and a bioinert synthetic material. We have observed that endothelial differentiation and migration were derived only on the gelatin-based matrix side, demonstrating that microengineered hydrogels can be used for spatially controlling stem cell behavior. In this paper, I will present our recent results in microscale technologies that can control the stem cell microenvironment.

Modulating stem cell microenvironment with microfabricated hydrogels

243rd National Meeting (2012)

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