Abstract

Intestine on a Chip for Basic Biology and Patient-Specific Medicine

Nancy L Allbritton, Professor, University Of North Carolina

Technical advances are making it possible to create tissue microenvironments on platforms that are compatible with high-content screening strategies. We have developed microfabricated devices to enable culture of organized cellular structures which possess much of the complexity and function of intact intestinal tissue.  Stem-cell culture enables single stem cells or intestinal crypts isolated from primary small or large intestine from humans or mice to grow and persist indefinitely as organotypic structures containing all of the expected lineages of the intestinal epithelium.  Our microengineered arrays and fluidic devices build on this knowledge base to reconstruct millimeter-scale primary intestinal epithelium that closely mimics the polarized 3D in vivo microarchitecture of the intestine Chemical gradients of growth and differentiation factors as well as cytokines are readily applied across the tissues. These bioanalytical platforms are envisioned as next generation systems for assay of microbiome-, drug- and toxin-interactions with the intestinal epithelia. Finally intestinal biopsy samples can be used to populate the constructs with cells producing patient-specific tissues for personalized medicine.