A 2D Intestinal Crypt Platform for Compound Screens - 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 I SBIR, this collaboration will generate 2D crypts with intervening regions of a
differentiated cell monolayer, optimize the platform with a focus on quantitative strategies to
benchmark performance, and perform small scale screens to demonstrate feasibility to advance
to a Phase 2 project. The goal is to develop and benchmark a quantitative in vitro method that will
enable investigators to efficiently evaluate the impact of compounds on intestinal stem cell
proliferation and differentiation.
