Intestinal extracellular matrix hydrogels to generate intestinal organoids for translational applications

Abstract

Intestinal organoids are emerging tools in intestinal disease modeling and regeneration. Matrigel, a basement membrane matrix extracted from mouse sarcoma, is the gold standard material for intestinal organoid culture. Yet, the tumor origin of this matrix does not effectively provide organoids with native intestine-like microenvironments. To overcome this limitation, we demonstrate a decellularized small intestine-derived hydrogel reinforced with three extracellular matrix (ECM) proteins that are essential for intestinal development. To identify optimal conditions for intestinal organoid culture, we optimized the concentrations of the ECM hydrogel derived from decellularized intestine and three ECM proteins. The intestinal organoids grown in the established ECM hydrogels have shown similarity to those grown in Matrigel in terms of organoid forming efficiency, size, and gene expression patterns of intestine-specific markers. Our intestine-mimetic hydrogel could increase the feasibility of intestinal organoids for more clinically relevant applications in disease modeling and regenerative medicine.