Development and Characterization of a Primary Ciliated Porcine Airway Model for the Evaluation of In Vitro Mucociliary Clearance and Mucosal Drug Delivery DOI Creative Commons
Janik Martin,

Veronika Neubauer,

Rebecca Rittersberger

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(4), P. 462 - 462

Published: April 2, 2025

Background/Objectives: In vitro models play a crucial role in preclinical respiratory research, enabling the testing and screening of mucosal formulations, dosage forms, inhaled drugs. Mucociliary clearance (MCC) is an essential defense mechanism drug delivery but often impaired diseases. Despite its importance, standardized MCC assays are rarely reported. Furthermore, many published methods primarily measure cilia beat frequency (CBF), which requires high-speed cameras that not accessible to all laboratories. Therefore, this study aimed develop physiologically relevant, differentiated model epithelium incorporates both beating functional MCC. We chose porcine airway mucosa as alternative human tissue due ethical considerations limited availability. The established designed provide reproducible method for broad range research Methods: previously tracheal primary cell (TMPC DS) model, derived from tissue, lacked presence cilia, effective analysis. For accurate assessment, they key mucus clearance. To address limitation, here-described ciliated (cTMPC) was developed. cTMPCs were isolated cultured under air–liquid interface (ALI) conditions 21 days promote differentiation. This evaluated morphology, tight junction formation, mucus-producing cells, barrier function, gene expression, tracer/IgG transport. model’s suitability assessed using inverted microscope. contrast TMPC DS thus could support analysis, cTMPC allows comprehensive studies. Results: developed demonstrated structural features epithelium, including well-differentiated integrity, function. Functional observed, confirming potential assays. Conclusions: closely replicates characteristics vivo airways. It provides valuable platform studying mucociliary clearance, toxicology, uptake, evaluating formulations forms research.

Language: Английский

Differential Responses of Pediatric and Adult Primary Epithelial Cells to Human Metapneumovirus and Respiratory Syncytial Virus Infection DOI Creative Commons

Pius I. Babawale,

Antonieta Guerrero-Plata

Viruses, Journal Year: 2025, Volume and Issue: 17(3), P. 380 - 380

Published: March 6, 2025

Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are pneumoviruses causing lower tract infections, primarily in infants children rather than healthy adults. bronchial epithelial cells serve as a viral replication target source of the innate immune response to these viruses. To better understand responses induced by RSV HMPV pediatric airway epithelium, we comparatively studied adult responses. We used normal human (NHBE) cultured an air–liquid interface culture system (ALI), which helps mimic architecture epithelium. Our results demonstrate differential patterns reduced interferons; inflammatory cytokines’ expression compared cells. However, expressed increased mucus stronger pro-inflammatory monocyte-derived dendritic These findings reveal age-dependent that may contribute more severe infections RSV.

Language: Английский

Citations

1
Modèles précliniques in vitro reproduisant l’épithélium respiratoire : application à l’étude de l’infection par le virus SARS-CoV-2 DOI

L. Morichon,

S. Assou,

A. Bourdin

et al.

Revue des Maladies Respiratoires, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Intrinsic OASL expression licenses interferon induction during influenza A virus infection DOI Creative Commons
Joel Rivera-Cardona, Tarun Mahajan,

Neeharika R. Kakuturu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Effective control of viral infection requires rapid induction the innate immune response, especially type I and III interferon (IFN) systems. Despite critical role IFN in host defense, numerous studies have established that most cells fail to produce IFNs response stimuli. The specific factors govern cellular heterogeneity potential during are not understood. To identify license some but others mount an infection, we developed approach for analyzing temporal scRNA-seq data influenza A virus (IAV)-infected cells. This identified expression several stimulated genes (ISGs) within pre-infection as correlates those cells, post-infection. Validation experiments confirmed intrinsic ISG OASL is essential robust IFNL IAV infection. Altogether, our findings reveal important IFN-independent, ISGs promoting provide new insights into mechanisms regulate cell-to-cell activation.

Language: Английский

Citations

0
Development and Characterization of a Primary Ciliated Porcine Airway Model for the Evaluation of In Vitro Mucociliary Clearance and Mucosal Drug Delivery DOI Creative Commons
Janik Martin,

Veronika Neubauer,

Rebecca Rittersberger

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(4), P. 462 - 462

Published: April 2, 2025

Background/Objectives: In vitro models play a crucial role in preclinical respiratory research, enabling the testing and screening of mucosal formulations, dosage forms, inhaled drugs. Mucociliary clearance (MCC) is an essential defense mechanism drug delivery but often impaired diseases. Despite its importance, standardized MCC assays are rarely reported. Furthermore, many published methods primarily measure cilia beat frequency (CBF), which requires high-speed cameras that not accessible to all laboratories. Therefore, this study aimed develop physiologically relevant, differentiated model epithelium incorporates both beating functional MCC. We chose porcine airway mucosa as alternative human tissue due ethical considerations limited availability. The established designed provide reproducible method for broad range research Methods: previously tracheal primary cell (TMPC DS) model, derived from tissue, lacked presence cilia, effective analysis. For accurate assessment, they key mucus clearance. To address limitation, here-described ciliated (cTMPC) was developed. cTMPCs were isolated cultured under air–liquid interface (ALI) conditions 21 days promote differentiation. This evaluated morphology, tight junction formation, mucus-producing cells, barrier function, gene expression, tracer/IgG transport. model’s suitability assessed using inverted microscope. contrast TMPC DS thus could support analysis, cTMPC allows comprehensive studies. Results: developed demonstrated structural features epithelium, including well-differentiated integrity, function. Functional observed, confirming potential assays. Conclusions: closely replicates characteristics vivo airways. It provides valuable platform studying mucociliary clearance, toxicology, uptake, evaluating formulations forms research.

Language: Английский

Citations

0