Abstract

Miniaturized Colon-on-Chip for Probiotic and Drug Screening

Nancy Allbritton, Frank and Julie Jungers Dean of the College of Engineering and Professor of Bioengineering, University of Washington in Seattle

Organ-on-chips are miniaturized devices that arrange living cells to simulate functional subunits of tissues and organs. These microdevices provide exquisite control of tissue microenvironment for the investigation of organ-level physiology and disease. Planar models enable high throughput screening with primary human intestinal epithelial cells- both stem/proliferative cells and differentiated zones. Compound screening for stimulation or inhibition of hormone secretion by enteroendocrine cells is of high value for therapeutic development given the role that hormones and neurotransmitters such as glucagon-like peptide 1 and serotonin play in regulating human feeding behavior and metabolism. These simple models can also be adapted to produce a thick, functional mucus layer with or without an oxygen gradient to create an anaerobic luminal surface for culture of colonic flora. Such devices are high of value in evaluating the impact of probiotics- a growing therapeutic area for the treatment of human disease. These planar systems can be modified to produce “flat crypts” with a stem/proliferative zone and differentiated cell region for the study of stem cell proliferation, lineage allocation and migration. Fully 3D polarized epithelium possess an array of crypt-like structures replicating the intestinal architecture. Imposition of chemical gradients across the crypt long axis yields a polarized epithelium with a cell migration from a stem-cell niche into a differentiated cell zone. This in vitro human colon crypt array replicates the architecture, luminal accessibility, tissue polarity, mucus layer, cell types and cellular responses of in vivo intestinal crypts. These bioanalytical systems provide both high throughput as well as low throughput/content rich platforms for assay of microbiome-behavior, drug-delivery, and other assays with a living human intestinal epithelium.