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Updated: Jan 24, 2026
10:51
Co-culture of Living Microbiome with Microengineered Human Intestinal Villi in a Gut-on-a-Chip Microfluidic Device
Published on: August 30, 2016
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Human Intestinal Morphogenesis Controlled by Transepithelial Morphogen Gradient and Flow-Dependent Physical Cues in a
Woojung Shin1, Christopher D Hinojosa2, Donald E Ingber3
1Department of Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
Iscience
|May 21, 2019
Summary
Physical cues like fluid flow and morphogen gradients drive intestinal villi formation. A human gut-on-a-chip model revealed Wnt signaling and flow regulation are key to this 3D morphogenesis.
Area of Science:
- Biomedical Engineering
- Developmental Biology
- Gastroenterology
Background:
- Intestinal morphogenesis is crucial for nutrient absorption and barrier function.
- Understanding the physical and biochemical cues regulating villi formation is essential for regenerative medicine.
Purpose of the Study:
- To investigate how physical cues (fluid flow, mechanical deformation) and morphogen gradients influence intestinal epithelial morphogenesis.
- To elucidate the molecular mechanisms underlying 3D villi-like structure formation using a human gut-on-a-chip model.
Main Methods:
- Utilized a human gut-on-a-chip microdevice with independent control of fluid flow and mechanical deformations.
- Cultured Caco-2 cells and primary epithelial cells under various flow conditions and static Transwell systems.
- Employed computational simulations to model and predict epithelial morphology and gene expression patterns.
Main Results:
- Both Caco-2 and primary epithelial cells formed 3D villi-like structures under apical and basal fluid flow.
- Cessation of basal flow led to the involution of preformed villi.
- Removal or dilution of basal medium in static Transwells also induced morphogenesis.
- Identified a transepithelial gradient of Dickkopf-1 (a Wnt antagonist) and flow-regulated Frizzled-9 receptor as key mediators of histogenesis.
Conclusions:
- Physical cues, particularly fluid flow and associated morphogen gradients, are critical regulators of intestinal morphogenesis.
- The human gut-on-a-chip model provides a powerful platform for studying stem cell biology and tissue development.
- Wnt signaling pathway modulation plays a significant role in flow-induced intestinal epithelial histogenesis.
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