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

Descrizione del progetto

Un nuovo modello di via aerea su chip per decodificare la tosse cronica

Attualmente, le opzioni terapeutiche per le persone che soffrono di tosse cronica sono limitate. Il progetto REVEAL, finanziato dal CER, mira quindi a sviluppare una via aerea su chip che imiti la biologia umana in modo più accurato rispetto ai modelli animali. Integrando cellule umane primarie e neuroni derivati da cellule staminali, i ricercatori ricreeranno il tratto respiratorio, compresa l’intricata innervazione e le cellule immunitarie. Grazie a questo approccio, gli scienziati studiano il modo in cui l’ipersensibilità neuronale inneschi la tosse persistente, fornendo una piattaforma per lo sviluppo di trattamenti personalizzati e screening di farmaci più efficaci. Lo strumento potrebbe inoltre rivoluzionare la ricerca su patologie come l’asma e le malattie polmonari ostruttive, nell’ambito di un metodo che sosterrà gli standard etici della ricerca riducendo il ricorso alla sperimentazione animale e accelerando la scoperta di terapie efficaci.

Obiettivo

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. 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. 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. We will develop a novel airway-on-a-chip that replicates the complex architecture of human airway tissue with innervation, immunocompetence, differentiated epithelium, and perfusable vascularization using primary cells and iPSC-derived neurons. The novel chip will facilitate high-throughput experiments. 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. The REVEAL model will help to reduce the burden of chronic cough by offering a better understanding of neuronal hypersensitivity in the airways. It will facilitate the development and testing of new drugs, offer a tool for personalized medicine, and provide 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. 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.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

HORIZON-ERC - HORIZON ERC Grants

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(si apre in una nuova finestra) ERC-2024-STG

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Istituzione ospitante

UNIVERSITAETSKLINIKUM AACHEN
Contributo netto dell'UE
€ 1 498 775,00
Indirizzo
Pauwelsstrasse 30
52074 Aachen
Germania
Regione
Nordrhein-Westfalen Köln Städteregion Aachen
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 1 498 775,00

Beneficiari (1)