Abstract

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

Nancy L Allbritton, Professor, University Of North Carolina

The ability to monitor and control the environment at the cellular and tissue level is one of the most promising applications for microengineered systems. Advances over the past decade in our ability to isolate and culture stem cells when combined with microengineering make it possible to conceive of physiologically functional systems that reconstitute whole organ physiology. These “organ-on-a-chip” platforms enable the establishment of the tissue interfaces necessary for organ function while providing exquisite control of experimental variables and sharing the richness of the intact organism. My group is at the forefront of marrying these advances in stem-cell culture with microengineering to create in vitro tissue mimics with a focus on the intestine. We constructed in vitro epithelium for human and mouse, small and large intestine that bear a stunning physical resemblance to the in vivo intestinal epithelium epithelia displaying arrays of polarized crypts. Most importantly this system recapitulates much of the physiology of the native intestinal epithelium. The system is constructed by developing a self-renewing monolayer of primary cells which is then shaped using microfabrication techniques. The platform enables application of the diverse chemical gradients (growth factors, morphogens, bacterial metabolites, food substances, and gases) thought to exist along the crypt-villus axis.  Application of gradients of microbiota-derived fermentation products across this tissue provided a direct demonstration that these products drive alterations in the size of the crypts’ proliferative and differentiated compartments as predicted to occur in vivo. The system also enables co-culture of anaerobic intestinal bacteria above a physiologic mucus layer. Using this platform, small intestinal biopsies from humans can be used to populate the constructs with cells producing patient-specific tissues for personalized medicine.