Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids

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Date
2018-02Type
- Journal Article
Citations
Cited 330 times in
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Cited 362 times in
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Abstract
Here we describe a method for fabricating a primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The primary epithelial cells are expanded as 3D organoids, dissociated, and cultured on a porous membrane within a microfluidic device with human intestinal microvascular endothelium cultured in a parallel microchannel under flow and cyclic deformation. In the Intestine Chip, the epithelium forms villi-like projections lined by polarized epithelial cells that undergo multi-lineage differentiation similar to that of intestinal organoids, however, these cells expose their apical surfaces to an open lumen and interface with endothelium. Transcriptomic analysis also indicates that the Intestine Chip more closely mimics whole human duodenum in vivo when compared to the duodenal organoids used to create the chips. Because fluids flowing through the lumen of the Intestine Chip can be collected continuously, sequential analysis of fluid samples can be used to quantify nutrient digestion, mucus secretion and establishment of intestinal barrier function over a period of multiple days in vitro. The Intestine Chip therefore may be useful as a research tool for applications where normal intestinal function is crucial, including studies of metabolism, nutrition, infection, and drug pharmacokinetics, as well as personalized medicine. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000244533Publication status
publishedExternal links
Journal / series
Scientific ReportsVolume
Pages / Article No.
Publisher
Nature Publishing GroupSubject
Biomimetics; Stem-cell biotechnology; Tissue engineeringMore
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Citations
Cited 330 times in
Web of Science
Cited 362 times in
Scopus
ETH Bibliography
yes
Altmetrics