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Sci Rep. 2018 Feb 13;8(1):2871. doi: 10.1038/s41598-018-21201-7.

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

Author information

1
Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
2
Emulate Inc., 27 Drydock Avenue, Boston, MA, 02210, USA.
3
Graduate program, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
4
Graduate program, Faculty of Biology, University of Freiburg, Freiburg, Germany.
5
Graduate program, Department of Bioengineering and iBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
6
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA.
7
Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA.
8
Division of Gastroenterology, Boston Children's Hospital, Boston, MA, 02115, USA.
9
Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA.
10
Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA. david.breault@childrens.harvard.edu.
11
Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA. david.breault@childrens.harvard.edu.
12
Harvard Stem Cell Institute, Harvard University, Boston, MA 02139, USA. david.breault@childrens.harvard.edu.
13
Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu.
14
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge 02139, MA, USA. don.ingber@wyss.harvard.edu.
15
Vascular Biology Program and Department Surgery, Boston Children's Hospital and Harvard Medical School, Boston 02115, MA, USA. don.ingber@wyss.harvard.edu.

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.

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