Development of an Advanced Airway-On-A-Chip Model to Investigate Neuronal Hypersensitivity in Chronic Cough

Introduction

Coughing is one of the most frequent reasons for physician appointments, and chronic coughing affects one in every 10 people in Europe. It has severe consequences on the patients’ quality of life. Treatment options are limited.

Background

Because animal models do not accurately replicate the human disease, the underlying mechanisms that trigger the onset of chronic coughing remain unclear, and several promising drug candidates have failed in clinical testing. Human in vitro models could overcome these hurdles if all relevant cell types are integrated.

Project Overview

In the REVEAL project, we will develop a comprehensive airway in vitro model to gain insight into the mechanisms underlying the onset and manifestation of neuronal hypersensitivity in chronic cough.

Airway-on-a-Chip Development

We will develop a novel airway-on-a-chip that replicates the complex architecture of human airway tissue with:

• Innervation
• Immunocompetence
• Differentiated epithelium
• Perfusable vascularization using primary cells and iPSC-derived neurons

The novel chip will facilitate high-throughput experiments.

Disease Models

Disease models will be created using cells from chronic cough patients, followed by the induction of inflammation. We will investigate neuroimmune interactions that trigger neuronal hypersensitivity and use the chip for drug screening.

Expected Outcomes

The REVEAL model will help to reduce the burden of chronic cough by offering a better understanding of neuronal hypersensitivity in the airways.

Benefits

It will facilitate:

1. The development and testing of new drugs
2. A tool for personalized medicine
3. A new approach methodology for risk assessment and toxicity testing

This will support the 3R principles, replacing and reducing animal testing in basic and applied research.

Broader Impact

The anticipated outcome of this project will also have an impact on other highly prevalent chronic airway diseases by providing a platform technology to study conditions such as asthma and chronic obstructive pulmonary disease (COPD), achieving a positive impact for many patients.