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Cultivate Primary Nasal Epithelial Cells from Children and Reprogram into Induced Pluripotent Stem Cells
Published on: March 10, 2016
A differentiated nasal epithelial cell model derived from children with acute wheeze and asthma
Rebecca L Watkinson1, Samuel T Montgomery2, Luke Berry3
1School of Allied Health, Curtin University, Perth, Australia; Wal-Yan Respiratory Research Centre, The Kids Research Institute Australia, Nedlands, Australia; Division of Paediatrics, School of Medicine, The University of Western Australia, Perth, Australia.
Insights
Researchers developed a new model of airway epithelium from children with acute wheeze and asthma (AWA). This model revealed underlying epithelial vulnerabilities, offering a platform to study AWA pathogenesis and test new therapies.
Area of Science:
- Pediatric respiratory research
- Epithelial biology
- Immunology
Background:
- The airway epithelium acts as a crucial barrier and immune regulator.
- Underlying epithelial weaknesses may predispose children to acute wheeze and asthma (AWA).
Purpose of the Study:
- To establish a differentiated in vitro model of pediatric AWA epithelium.
- To investigate epithelial vulnerabilities and responses during AWA exacerbations.
Main Methods:
- Assessed the feasibility of creating a differentiated nasal epithelial cell model from children with AWA.
- Examined mucociliary differentiation, barrier function, viral receptor expression, and cytokine profiles.
Main Results:
- Successfully established a differentiated pediatric AWA epithelial model reflecting patient heterogeneity.
- The AWA model showed increased barrier permeability, higher rhinovirus receptor (ICAM1) expression, elevated pro-inflammatory/antiviral cytokines, and potentially reduced cilia.
- Identified correlations between clinical data and epithelial parameters.
Conclusions:
- A differentiated epithelial model of pediatric AWA was successfully created, highlighting inherent epithelial vulnerabilities.
- This model serves as a valuable platform for investigating AWA pathogen interactions, disease origins, and therapeutic strategies.
Background:
The airway epithelium is the primary structural and functional airway barrier and orchestrates innate immunity. Some children may have underlying epithelial vulnerabilities that contribute to the pathogenesis of acute wheeze and asthma (AWA).
Objective:
To investigate the pediatric AWA epithelial environment and responses at time of exacerbation to elucidate cellular vulnerabilities; thus, a differentiated in vitro model with differentiated cell types is required.
Methods:
Here, feasibility of establishing a differentiated model of primary nasal epithelial cells from children presenting to hospital with AWA was assessed. This was followed by examination of mucociliary differentiation, barrier integrity and function, viral receptor expression, and appropriate pro-inflammatory and antiviral cytokines compared with nasal epithelial cells derived from children who were non-wheezing non-atopic and non-wheezing with positive atopy.
Results:
A differentiated pediatric AWA model was established with interparticipant heterogeneity reflected appropriately. The AWA model was of epithelial lineage and had mucociliary differentiation, barrier integrity and function, viral receptor expression, and the production of innate immune cytokines. However, the AWA epithelium had a more permeable paracellular barrier, higher expression of rhinovirus receptor ICAM1, intrinsically higher levels of pro-inflammatory and antiviral cytokines IL-6, IL-8, CCL5, CXCL10, and IFNL1, and potentially fewer cilia. Relationships between demographic and clinical data and AWA epithelial parameters were also identified.
Conclusion:
Collectively, a differentiated epithelial model of pediatric AWA was established, and results indicated underlying epithelial vulnerabilities in these children. This platform may be used to investigate the role of the AWA epithelium in pathogen infections, disease etiology, and therapeutic pipelines.
