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.
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