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Cited by 185

The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.

Formation of Human Colonic Crypt Array by Application of Chemical Gradients Across a Shaped Epithelial Monolayer

Open access
Wang, Yuli, Kim, Raehyun, Gunasekara, Dulan B., Reed, Mark I., DiSalvo, Matthew, Nguyen, Daniel L., Bultman, Scott J., Sims, Christopher E., Magness, Scott T., Allbritton, Nancy L.·2018·Cellular and Molecular Gastroenterology and Hepatology

Abstract

BACKGROUND & AIMS: The successful culture of intestinal organoids has greatly enhanced our understanding of intestinal stem cell physiology and enabled the generation of novel intestinal disease models. Although of tremendous value, intestinal organoid culture systems have not yet fully recapitulated the anatomy or physiology of the in vivo intestinal epithelium. The aim of this work was to re-create an intestinal epithelium with a high density of polarized crypts that respond in a physiologic manner to addition of growth factors, metabolites, or cytokines to the basal or luminal tissue surface as occurs in vivo. METHODS: A self-renewing monolayer of human intestinal epithelium was cultured on a collagen scaffold microfabricated with an array of crypt-like invaginations. Placement of chemical factors in either the fluid reservoir below or above the cell-covered scaffolding created a gradient of that chemical across the growing epithelial tissue possessing the in vitro crypt structures. Crypt polarization (size of the stem/proliferative and differentiated cell zones) was assessed in response to gradients of growth factors, cytokines, and bacterial metabolites. RESULTS: Chemical gradients applied to the shaped human epithelium re-created the stem/proliferative and differentiated cell zones of the in vivo intestine. Short-chain fatty acids applied as a gradient from the luminal side confirmed long-standing hypotheses that butyrate diminished stem/progenitor cell proliferation and promoted differentiation into absorptive colonocytes. A gradient of interferon-γ and tumor necrosis factor-α significantly suppressed the stem/progenitor cell proliferation, altering crypt formation. CONCLUSIONS: The in vitro human colon crypt array accurately mimicked the architecture, luminal accessibility, tissue polarity, cell migration, and cellular responses of in vivo intestinal crypts.

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Metadata

Authors
Wang, Y., Kim, R., Gunasekara, D. B., Reed, M. I., DiSalvo, M., Nguyen, D. L., Bultman, S. J., Sims, C. E., Magness, S. T., & Allbritton, N. L.
Venue
Cellular and Molecular Gastroenterology and Hepatology
Publisher
Elsevier BV
Published
2018
Volume
5
Issue
2
Pages
113-130
ISSN
2352-345X (ISSN-L)
OpenAlex
W2766670989
Cited by
185
References
14
FWCI
15.92
Type
journal article
Language
en
Open access
gold

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Wang, Y., Kim, R., Gunasekara, D. B., Reed, M. I., DiSalvo, M., Nguyen, D. L., Bultman, S. J., Sims, C. E., Magness, S. T., & Allbritton, N. L. (2018). Formation of Human Colonic Crypt Array by Application of Chemical Gradients Across a Shaped Epithelial Monolayer. Cellular and Molecular Gastroenterology and Hepatology. https://doi.org/10.1016/j.jcmgh.2017.10.007

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.