Three-Dimensional Morphogenesis in Canine Gut-on-a-Chip Using Intestinal Organoids Derived from Inflammatory Bowel Disease Patients

Itsuma Nagao; Meg Nakazawa; Yoko M. Ambrosini

doi:10.3791/65720

Morfogenesi tridimensionale nell'intestino su chip canino utilizzando organoidi intestinali deriv...

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Three-Dimensional Morphogenesis in Canine Gut-on-a-Chip Using Intestinal Organoids Derived from Inflammatory Bowel Disease Patients

Morfogenesi tridimensionale nell'intestino su chip canino utilizzando organoidi intestinali derivati da pazienti con malattie infiammatorie intestinali

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February 9, 2024

DOI: 10.3791/65720-v

Itsuma Nagao^1,2, Meg Nakazawa¹, Yoko M. Ambrosini¹

¹Department of Veterinary Clinical Sciences, College of Veterinary Medicine,Washington State University, ²Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences,The University of Tokyo

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Overview

This study focuses on the integration of canine intestinal organoids with a Gut-on-a-Chip microfluidic system, providing a relevant model for human intestinal diseases. The protocols developed facilitate 3D morphogenesis and dynamic in vitro modeling of the gut, contributing to the advancement of treatments for intestinal diseases in both dogs and humans.

Key Study Components

Area of Science

Neuroscience
Comparative Medicine
Microfluidics

Background

Intestinal cellular morphogenesis is crucial for understanding gut health.
Traditional models often fail to accurately represent human processes.
Canine models provide a closer approximation to human intestinal diseases.
The One Health Initiative emphasizes the interconnectedness of human and animal health.

Purpose of Study

To develop a replicable model for studying intestinal morphogenesis.
To explore host-microbiome interactions and their implications for health.
To facilitate drug and probiotic screenings in a comparative context.

Methods Used

Preparation of the Gut-on-a-Chip device with ECM coating.
Seeding of canine intestinal organoids into the microfluidic system.
Application of continuous flow and cyclic strain to mimic physiological conditions.
Immunofluorescent staining to assess the 3D structure and barrier function.

Main Results

Successful establishment of 3D morphogenesis in the microfluidic system.
Observation of villus-like structures and functional intestinal barriers.
Demonstrated potential for comparative studies in intestinal diseases.
Validated the model for future translational research.

Conclusions

The Gut-on-a-Chip model is a promising tool for studying intestinal health.
Integration of canine organoids enhances the relevance of findings.
This approach aligns with the One Health perspective, benefiting both human and animal health.

Frequently Asked Questions

What is the significance of using canine intestinal organoids?

Canine intestinal organoids provide a closer model to human intestinal diseases, facilitating more relevant research.

How does the Gut-on-a-Chip system work?

The Gut-on-a-Chip system mimics the intestinal environment, allowing for dynamic studies of cellular interactions and morphogenesis.

What are the applications of this research?

This research can be applied to drug testing, understanding gut diseases, and exploring microbiome interactions.

What challenges were faced in this study?

Challenges included achieving uniform ECM coating and ensuring proper cell attachment in the microfluidic system.

How does this study contribute to the One Health Initiative?

It emphasizes the interconnectedness of human and animal health by using a canine model to study human diseases.

What future research directions does this study suggest?

Future research could explore more complex disease models and the effects of various treatments on intestinal health.

L'integrazione di organoidi intestinali canini e di un sistema microfluidico Gut-on-a-Chip offre modelli traslazionali rilevanti per le malattie intestinali umane. I protocolli presentati consentono la morfogenesi 3D e la modellazione dinamica in vitro dell'intestino, aiutando nello sviluppo di trattamenti efficaci per le malattie intestinali nei cani e negli esseri umani con One Health.

Il nostro obiettivo di ricerca è quello di creare un metodo per la crescita di strutture 3D utilizzando cellule intestinali di animali simili all'uomo, in particolare cani. La morfogenesi cellulare intestinale è stata ampiamente studiata attraverso modelli animali da laboratorio, che sono costosi, richiedono tempo e non rappresentano accuratamente i processi di sviluppo umano. Inoltre, i modelli statici convenzionali di coltura cellulare 2D non sono in grado di imitare la complessa organizzazione spaziale di un'architettura 3D abSerial.

Ottenere l'adesione di singole cellule derivate da organoidi intestinali sulla superficie PDMS rivestita di ECM ha rappresentato una sfida significativa. Un passo fondamentale nell'affrontare questa sfida, sia per garantire un rivestimento ECM uniforme attraverso l'attivazione superficiale che per consentirne l'asciugatura durante la notte. L'integrazione della tecnologia degli organoidi canini derivati dal paziente con la morfogenesi 3D in vitro offre una strada promettente per condurre ricerche traslazionali sulle malattie croniche multifattoriali, in linea con l'iniziativa One Health.

Il protocollo per l'IBD canina, ottenuto su un chip, offre un modello replicabile per la medicina comparata, consentendo studi sulla morfogenesi intestinale, sulle interazioni ospite-microbioma, sulle infezioni, sugli screening di farmaci e probiotici e ha un'applicabilità interspecie.

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