Designer matrices for intestinal stem cell and organoid culture

Here the authors used modular synthetic hydrogel (cross-linked poly(ethylene glycol) (PEG)) to define the key extracellular matrix (ECM) parameters that govern intestinal stem cell (ISC) expansion and organoid formation, and show that separate stages of the process require different mechanical environments and ECM components. Fibronectin-based adhesion was sufficient for ISC survival and proliferation and high matrix stiffness significantly enhanced ISC expansion through a yes-associated protein 1 (YAP)-dependent mechanism. ISC differentiation and organoid formation, on the other hand, required a soft matrix and full-length laminin-111-based adhesion. The authors also produced mechanically dynamic matrices that were initially optimal for ISC expansion and subsequently permissive to differentiation and intestinal organoid formation.