Journal
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 3, Issue 10, Pages 2502-2513Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.7b00368
Keywords
intestinal epithelial stem cells; differentiation; intestine-on-a-chip; microfabrication; gradient; tissue mimics
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Funding
- National Institutes of Health [R01DK109559]
- National Science Foundation [ECCS-1542015]
- National Nanotechnology Coordinated Infrastructure (NNCI)
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Organoid culture has had a significant impact on in vitro studies of the intestinal epithelium; however, the exquisite architecture, luminal accessibility, and lineage compartmentalization found in vivo has not been recapitulated in the organoid systems. We have used a microengineered platform with suitable extracellular matrix contacts and stiffness to generate a self-renewing mouse colonic epithelium that replicates key architectural and physiological functions found in vivo, including a surface lined with polarized crypts. Chemical gradients applied to the basal-luminal axis compartmentalized the stem/progenitor cells and promoted appropriate lineage differentiation along the in vitro crypt axis so that the tissue possessed a crypt stem cell niche as well as a layer of differentiated cells covering the luminal surface. This new approach combining microengineered scaffolds, native chemical gradients, and biophysical cues to control primary epithelium ex vivo can serve as a highly functional and physiologically relevant in vitro tissue model.
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