Intestine on Chip for Normal Physiology and Disease Models
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. A 3D polarized
epithelium using primary human or mouse gastrointestinal stem cells was
developed to fully recapitulate gastrointestinal epithelial architecture
and physiology. A planar monolayer comprised of stem/proliferative and
differentiated primary cells is cultured on a shaped hydrogel scaffold
with 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 stem-cell niche and
differentiated cell zone. The stem cells proliferate, migrate and
differentiate along the crypt axis as they do in vivo. A dense mucus
layer is formed on the luminal epithelial surface that is impermeable to
bacteria and acts a barrier to toxins. An oxygen gradient across the
tissue mimic permits luminal culture of anaerobic bacteria while
maintaining an oxygenated stem cell niche. This in vitro human colon
crypt array replicates the architecture, luminal accessibility, tissue
polarity, cell migration, and cellular responses of in vivo intestinal
crypts. A thick impenetrable layer of mucus with biophysical parameters
similar to that of a living human can be formed for epithelial
cell-microbe studies. Intestinal biopsy samples can be used to populate
these constructs to produce patient-specific tissues for personalized
medicine and disease modeling. This bioanalytical platform is envisioned
as a next-generation system for assay of microbiome-behavior,
drug-delivery and toxin-interactions with the intestinal epithelia.
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