Modeling Bronchial Epithelium in Severe Asthma With Human Induced Pluripotent Stem Cells (iPSC) — MOSAIC  

Severe Asthma Clinical Trial

Official title: Modeling Bronchial Epithelium in Severe Asthma With Human Induced Pluripotent Stem Cells (iPSC)

Status Completed

Clinical Trial Summary

Asthma is severe when it cannot be controlled with maximum-dose inhaled therapies while management of comorbidities and other precipitating or aggravating factors has been optimized. Allergic bronchopulmonary aspergillosis (ABPA) is a complex bronchopulmonary disease resulting from immunological reactions against Aspergillus Fumigatus.

The development of a model of bronchial epithelium generated from patients with chronic lung disease will allow the modeling of bronchial tissue to understand the formation of these mucus plugs. This study aims to validate this model

The investigators propose to verify the feasibility of obtaining and comparing two epithelia in two populations based on the following experiments:

Differentiation of an Induced Pluripotent Stem cell (iPSC) clone derived from blood sample (Peripheral Blood Mononuclear Cells) of Type 2 inflammation (T2) severe asthma and Allergic Bronchopulmonary Aspergillosis (ABPA) in order to obtain differentiated bronchial epithelia in vitro.

Clinical Trial Description

Asthma is severe when it cannot be controlled with maximum-dose inhaled therapies while management of comorbidities and other precipitating or aggravating factors has been optimized. Allergic bronchopulmonary aspergillosis (ABPA) is a complex bronchopulmonary disease resulting from immunological reactions against Aspergillus Fumigatus.

At the cellular and molecular level, severe asthma and ABPA are chronic bronchial diseases characterized by type 2 (T2) airway inflammation, bronchial smooth muscle hyperplasia, excessive mucus production by mucus cell metaplasia and epithelial remodeling. Type 2 inflammation in asthma is predominant and is characterized by the accumulation of immune cells, such as eosinophils, mast cells, T-helper 2 (Th2) cells, innate lymphoid cells type 2 (ILC2s) and dendritic cells.

Persistent airway obstruction despite maximal therapy is currently considered the greatest unmet medical need in asthma treatment. Fahy and colleagues published a key paper in 2018 that may explain airway obstruction. Using chest CT scans, they demonstrated the presence of mucus plugs that completely occlude segments of the airways of severe asthmatics. These mucus plugs are associated with a high number of circulating eosinophils in the blood.

There is no large-scale model to model severe asthma and ABPA. The investigators propose to develop a bronchial epithelium with pluripotent stem cells (iPSC) in air-liquid interface called iALI generated from these patients in aim to model severe asthma and ABPA and in particular the epithelium.

The secondary objectives aims to answer are:

• Comparison of the iPSC derived airway epithelium with nasal epithelial cells isolated from the same patient (nasal brush).

• To characterize the phenotype of the iPSC derived airway epithelium from ABPA and T2 severe asthma patient, in comparison to a healthy control.

• Differentiation of iPSC into mature eosinophils

• Co culture of the epithelia with iPSC derived eosinophils

• Culture of iPSC derived airway epithelium with Charcot-Leyden crystal

• Demonstrate the feasibility of obtaining iPSC from peripheral blood sampling. ;

Related Conditions & MeSH terms

• Allergic Bronchopulmonary Aspergillosis (ABPA)
• Aspergillosis
• Asthma
• Pulmonary Aspergillosis
• Severe Asthma

• NCT number: NCT05616338
• Study type: Interventional
• Source: University Hospital, Montpellier
• Status: Completed
• Phase: N/A
• Start date: November 29, 2022
• Completion date: March 16, 2023