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Published on: May 24, 2024
A microfluidic chip based model for the study of full thickness human intestinal tissue using dual flow
1Faculty of Life Sciences, University of Hull , Cottingham Road, Hull HU6 7RX, United Kingdom.
Insights
This study introduces a novel microfluidic device for maintaining human intestinal tissue viability ex vivo. This advanced model aids in studying inflammatory bowel diseases like Ulcerative Colitis and Crohn's Disease.
Area of Science:
- Gastroenterology and Biomedical Engineering
- Development of advanced organ-on-a-chip technologies for human disease modeling
Background:
- Current inflammatory bowel disease (IBD) research relies on animal and cell models, which fail to fully replicate human pathophysiology.
- Limitations in existing models hinder the accurate study of complex diseases like Ulcerative Colitis and Crohn's Disease.
Purpose of the Study:
- To present a novel dual flow microfluidic device for ex vivo culture of full-thickness human intestinal tissue.
- To establish a more accurate human model for studying IBD biology and therapeutic interventions.
Main Methods:
- Utilized a dual flow microfluidic device to perfuse human intestinal tissue ex vivo for up to 72 hours.
- Assessed tissue viability and integrity using Haematoxylin & Eosin staining, immunohistochemistry, and lactate dehydrogenase release assays.
- Measured calprotectin levels to confirm the maintenance of an inflammatory state within the tissue.
Main Results:
- The microfluidic device successfully maintained the viability and integrity of human intestinal tissue ex vivo.
- Demonstrated sustained inflammatory markers (calprotectin) in the tissue after perfusion.
- Confirmed tissue structural integrity through histological and biochemical analyses.
Conclusions:
- The developed microfluidic device provides a viable platform for ex vivo human intestinal tissue culture.
- This human-centric model offers a significant advancement for studying inflammatory bowel disease.
- The model is poised to be valuable for investigating disease mechanisms and testing new treatments for IBD.
Abstract:
The study of inflammatory bowel disease, including Ulcerative Colitis and Crohn's Disease, has relied largely upon the use of animal or cell culture models; neither of which can represent all aspects of the human pathophysiology. Presented herein is a dual flow microfluidic device which holds full thickness human intestinal tissue in a known orientation. The luminal and serosal sides are independently perfused ex vivo with nutrients with simultaneous waste removal for up to 72 h. The microfluidic device maintains the viability and integrity of the tissue as demonstrated through Haematoxylin & Eosin staining, immunohistochemistry and release of lactate dehydrogenase. In addition, the inflammatory state remains in the tissue after perfusion on the device as determined by measuring calprotectin levels. It is anticipated that this human model will be extremely useful for studying the biology and testing novel interventions in diseased tissue.

