Niche-inspired synthetic matrices for epithelial organoid culture

• DOI: 10.1101/806919
• Publication Date: 2019-10-16T13:59:44Z
• Authors: Victor Hernandez-...; Timothy Kassis; Arinola Lampejo; GiHun Choi; Mario E. Gamboa; Juan S. Gnecco; David T. Breault; Rebecca Carrier; Linda G. Griffith
• Keywords: Organoid; Matrigel; Matrix (chemical analysis); Regenerative Medicine

Abstract Epithelial organoids are now an important tool in fields ranging from regenerative medicine to drug discovery. Organoid culture requires Matrigel, a complex, tumor-derived, extracellular matrix. An alternative completely synthetic matrix could improve reproducibility, clarify mechanistic phenomena, and enable applications involving human implantation. Here, we designed matrices with tunable biomolecular biophysical properties that allowed us identify critical gel parameters organoid formation. Inspired by known epithelial integrin expression the proliferative niche of intestine, identified α2β1 integrin-binding peptide as component supports duodenal colon endometrial propagation. We show emerge single cells, retain their capacity, functionally responsive basolateral stimulation have correct apicobasal polarity upon induction differentiation. The local presentation cues, rather than bulk mechanical properties, appears be dominant parameter governing cell proliferation formation