Intestinal stem cells (ISCs) can self-organize to form complex, three-dimensional organoids that replicate many aspects of the native intestine, including its functionality. Intestinal organoid models hold great promise as a tool to study intestinal development and disease, screen drug candidates, or produce transplantable tissue. However, the factors that mediate self-organization from cell to colony to organoid are not yet well understood. Current culture methods for growth of intestinal organoids rely almost exclusively on Matrigel. However, Matrigel’s loosely-defined and variable composition makes clinical translation nearly impossible and limits investigations into the role of matrix factors on organoid formation.
To address the issues associated with culture in Matrigel, we propose to develop innovative, hydrogel scaffolds for adult intestinal stem cells and use them to study and optimize their expansion, colony formation, and differentiation to form organoids. Specifically, we are investigating if crypt formation can be spatiotemporally controlled by using patterned or bulk photo-degradation. Once a synthetic scaffolding system is developed, I am interested in applying the platform to test hypothesis related to ISC mechanosensing and to develop a drug screening platform for various gastrointestinal diseases.
Figure 1. Micrograph of ISC colonies in 630 Pa hydrogels 4 days after seeding with single stem cells. Scale bar 100 mm.