A 2D Intestinal Crypt Platform for Compound Screens

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PROJECT SUMMARY Intestinal epithelium is the fastest dividing tissue in the body, and the health of the cells can be easily impacted by environmental toxins and drugs. This organ system is therefore a prime target for biological testing of medicinal compounds, prebiotics, and microbial products. An in vitro gut model that can precisely predict these impacts will reduce the burden of testing by diminishing reliance on animal models, minimizing the number of overlapping assessments and helping to eliminate unnecessary testing. To meet this need, Altis Biosystems Inc., an early stage biotechnology company, will collaborate with scientists at University of Washington to develop a novel 2-dimensional (2D) crypt platform that emulates the gut epithelium. Human primary intestinal epithelial stem cells will be patterned on the platform to mimic a gut epithelium possessing a stem-cell niche, and migratory proliferating and differentiating cells. This planar 2D platform will enable high-content/high-throughput assays in a rugged and reproducible manner. In this Phase II SBIR, this collaboration will generate a commercial 2D crypts organ-on-a-chip platform using established 12-well plates and expand the platform to incorporate a 96-well plate high-content format. In addition, the commercial platform will be benchmarked in collaboration with AstraZeneca’s oncology safety team as a predictive assay system for intestinal off-target effects