| Title: |
Unveiling Pathological Insights and Accelerating Antiviral Drug Discovery in Respiratory Viral Infections with Polarized Organoids |
| Authors: |
Alessandri-Gradt, Elodie; Hubert, Mathieu; Archambault, Flora; Tombette, Fabienne; Cambet, Yves; Constant, Samuel; Ar Gouilh, Meriadeg, M.; Plantier, Jean-Christophe; Benard, Magalie; Galas, Ludovic; Tapparel, Caroline |
| Contributors: |
Dynamique Microbienne associée aux Infections Urinaires et Respiratoires (DYNAMICURE); Université de Caen Normandie (UNICAEN); Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN); Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM); Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0); Normandie Université (NU); Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0); Université de Rouen Normandie (UNIROUEN); Normandie Université (NU)-Normandie Université (NU); Service de Virologie CHU Caen; CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie (CHU Caen Normandie); Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN); Université de Rouen Normandie |
| Source: |
Pathways to Precision Medicine ; https://hal.science/hal-05267358 ; Pathways to Precision Medicine, Apr 2025, Rouen (France), France |
| Publisher Information: |
CCSD |
| Publication Year: |
2025 |
| Collection: |
Normandie Université: HAL |
| Subject Terms: |
Organoids; Precision medicine; [SDV]Life Sciences [q-bio] |
| Subject Geographic: |
France |
| Time: |
Rouen (France), France |
| Description: |
International audience ; Over the past decade, organoid models have not only emerged as an innovative research model but also as a valuable tool in precision medicine, particularly in the field of respiratory diseases. These three-dimensional in vitro models can replicate the complex architecture of human tissues, providing opportunities to predict drug response. This is especially critical in the context of respiratory viruses for which effective antiviral treatments are often lacking. Moreover, respiratory organoids generated from individual human primary cells could revolutionize our understanding of pulmonary diseases like asthma, chronic obstructive pulmonary disease (COPD), or cystic fibrosis (CF).This work aims to explore the role of respiratory organoids in precision medicine, focusing on their application in studying viral respiratory infection and their potential to personalize treatment approaches for patients.Primary respiratory epithelial cells of asthmatic and healthy donors were cultured in human airway epithelial cell medium (Epithelix) to achieve 70-80% confluence. Aggregates were formed in Aggrewell™400 plate using PneumaCult™ medium (Stemcell) and cultured for 15 days without matrigel, to obtain full maturation of apical out epithelial polarization. Three main aspects were addressed: 1) immunostaining and confocal microscopy imaging (Stellaris Leica) to confirm the asthmatic phenotype in polarized organoids, 2) infection with respiratory syncytial virus (RSV), a major cause of asthma exacerbation, to monitor viral replication kinetic by qPCR up to day 8 post-infection, 3) the scalability of organoids model in a high-throughput format for anti-RSV drug screening assayRespiratory organoids sizes ranged from 50 μm to 150 μm, with effective motility at day 15 due to external cilia beating. Confocal imaging confirmed the presence of ciliated, basal and mucus cells in asthma organoids, similar to healthy control. RSV infection (0.03 MOI for 2h at 37°C with 5% CO2) led to increased viral replication, ... |
| Document Type: |
conference object; still image |
| Language: |
English |
| Availability: |
https://hal.science/hal-05267358; https://hal.science/hal-05267358v1/document; https://hal.science/hal-05267358v1/file/P2M2025_Poster_organoids_20250307.pdf |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.6E50754B |
| Database: |
BASE |