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

Descripción del proyecto

Nuevo modelo de vías respiratorias en un chip para descifrar la tos crónica

En la actualidad, las opciones de tratamiento para las personas que padecen tos crónica son limitadas. El equipo del proyecto REVEAL, financiado por el Consejo Europeo de Investigación, pretende desarrollar vías respiratorias en un chip que imiten la biología humana con más precisión que los modelos animales. Mediante la integración de células humanas primarias y neuronas derivadas de células madre, los investigadores recrearán las vías respiratorias, incluida la intrincada inervación y las células inmunitarias. Con este método, los científicos investigan cómo la hipersensibilidad neuronal desencadena la tos persistente, lo que proporcionará una plataforma para tratamientos personalizados y un cribado de fármacos más eficaz. La herramienta también podría revolucionar la investigación de afecciones como el asma y la enfermedad pulmonar obstructiva. En última instancia, este planteamiento respaldará las normas éticas de investigación al reducir la dependencia de los ensayos con animales y acelerar al mismo tiempo el descubrimiento de tratamientos eficaces.

Objetivo

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.