Nonadhesive Alginate Hydrogels Support Growth of Pluripotent Stem Cell-Derived Intestinal Organoids

Abstract

Summary: Human intestinal organoids (HIOs) represent a powerful system to study human development and are promising candidates for clinical translation as drug-screening tools or engineered tissue. Experimental control and clinical use of HIOs is limited by growth in expensive and poorly defined tumor-cell-derived extracellular matrices, prompting investigation of synthetic ECM-mimetics for HIO culture. Since HIOs possess an inner epithelium and outer mesenchyme, we hypothesized that adhesive cues provided by the matrix may be dispensable for HIO culture. Here, we demonstrate that alginate, a minimally supportive hydrogel with no inherent cell instructive properties, supports HIO growth in vitro and leads to HIO epithelial differentiation that is virtually indistinguishable from Matrigel-grown HIOs. In addition, alginate-grown HIOs mature to a similar degree as Matrigel-grown HIOs when transplanted in vivo, both resembling human fetal intestine. This work demonstrates that purely mechanical support from a simple-to-use and inexpensive hydrogel is sufficient to promote HIO survival and development. : Spence and colleagues identify alginate as a nonadhesive growth matrix to support human intestinal organoid culture. Their results demonstrate that alginate-grown HIOs are virtually indistinguishable from traditional Matrigel-grown HIOs both in vitro and in vivo. This work increases the translational potential of HIOs by eliminating reliance on cell-derived matrices and reducing cost. Keywords: intestine, alginate, hydrogel, human pluripotent stem cell, organoid, intestinal organoid, enteroid