Synthetic Hydrogel System for Growth of Intestinal Organoids

A process for using artificial hydrogel matrices to grow miniature organs (organoids) derived from stem cell precursors was described in a recent paper.

The full potential of organoids in research and therapy has remained unrealized, owing to the poorly defined animal-derived matrices in which they are grown. To eliminate this shortcoming, investigators at the Ecole Polytechnique Fédérale de Lausanne (Switzerland) used modular synthetic hydrogel networks to define the key extracellular matrix (ECM) parameters that governed intestinal stem cell (ISC) expansion and organoid formation. The patent-pending hydrogels were fabricated from water, polyethylene glycol, and ECM components such as fibronectin.

The investigators reported in the November 16, 2016, online edition of the journal Nature that separate stages of the organoid growth process required different mechanical environments and ECM components. In particular, fibronectin-based adhesion was sufficient for ISC survival and proliferation. 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 laminin-based adhesion.

The investigators used these insights to build a fully defined culture system for the expansion of mouse and human ISCs. They also produced mechanically dynamic matrices that were initially optimal for ISC expansion and then subsequently permissive to differentiation and intestinal organoid formation, thus creating well-defined alternatives to animal-derived matrices for the culture of mouse and human stem-cell-derived organoids.

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Ecole Polytechnique Fédérale de Lausanne