Modeling Bronchial Epithelium Modifications Associated With COPD Using iPS

Completed

• Conditions: Smoking; Pulmonary Disease, Chronic Obstructive
• Interventions: Procedure: Bronchial biopsy; Procedure: Skin biopsy; Procedure: Blood sample

• Registration Number: NCT03181204
• Lead Sponsor: University Hospital, Montpellier

Brief Summary

The primary objective of this study is to 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 (iPS) clone derived from cutaneous biopsy in a population of heavy smokers (plus patients with chronic obstructive pulmonary disease) in order to obtain differentiated bronchial epithelia in vitro.

* For each of these same patients, generation of bronchial epithelium in vitro from bronchial biopsy using human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures.

Detailed Description

Secondary objectives:

* Confrontation of the two models of in vitro generation of bronchial epithelium by iPS and ALI in order to validate our model of study of the human bronchial epithelium COPD generated by the iPS.

* Inducing a "COPD-like" epithelial phenotype by exposing the bronchial epithelia generated from the iPS to a source of in vitro toxin (tobacco) and studying its effects by transcriptomic analysis via high-throughput sequencing (NGS) at key steps during the model.

* Demonstrate the feasibility of obtaining iPS from peripheral blood sampling.

Study Timeline

• Study First Submitted: 2017-06-06
• Study First Submitted QC: 2017-06-06
• Study First Posted: 2017-06-08
• Study Start: 2017-08-07
• Primary Completion: 2022-03-09
• Study Completion: 2022-03-09
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-07
• Last Update Posted: 2023-09-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

Not provided

Exclusion Criteria

• Contra-indication for bronchial fibroscopy and cutaneous biopsy
• Deficiency in α-1 antitrypsin
• Significant bronchiectasis on chest computed tomography scan
• Colonization of the airways by Pseudomonas Aeroginosa or Aspergillus
• Chemotherapy or other cytotoxic treatments in the last 12 months
• Systemic corticotherapy in the 4 weeks prior to inclusion
• Long-term antibiotic treatment, notably by macrolides
• Any other treatment that may affect the bronchial epithelium, this being left to the discretion of the investigating physician
• Consumer of illicit drugs or alcohol
• Participant in an exclusion period determined by a previous study
• Subject not affiliated with, or not beneficiary of, a social security plan.
• Pregnant or nursing women according to Article L1121-5 of the Public Health Code.
• Vulnerable persons according to Article L1121-6 of the Public Health Code
• An adult who is protected or incapable of giving consent in accordance with Article L1121-8 of the Public Health Code
• Subject deprived of freedom by judicial or administrative decision.
• Those patients for whom two epithelia cultures (1 from bronchial biopsy ("ALI") and 1 from fibroblast reprogrammation of redifferentiated iPS ("iALI")) were not obtained will be excluded (post-inclusion).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients likely to develop COPD	Bronchial biopsy	Patients in this group are relatively light smokers who have developed chronic obstructive lung disease (COPD). Intervention: Bronchial biopsy Intervention: Skin biopsy Intervention: Blood sample
Patients not likely to develop COPD	Skin biopsy	Patients in this group are heavy smokers who have no signs of chronic obstructive lung disease (COPD). Intervention: Bronchial biopsy Intervention: Skin biopsy Intervention: Blood sample
Patients not likely to develop COPD	Blood sample	Patients in this group are heavy smokers who have no signs of chronic obstructive lung disease (COPD). Intervention: Bronchial biopsy Intervention: Skin biopsy Intervention: Blood sample
Patients likely to develop COPD	Blood sample	Patients in this group are relatively light smokers who have developed chronic obstructive lung disease (COPD). Intervention: Bronchial biopsy Intervention: Skin biopsy Intervention: Blood sample
Patients not likely to develop COPD	Bronchial biopsy	Patients in this group are heavy smokers who have no signs of chronic obstructive lung disease (COPD). Intervention: Bronchial biopsy Intervention: Skin biopsy Intervention: Blood sample
Patients likely to develop COPD	Skin biopsy	Patients in this group are relatively light smokers who have developed chronic obstructive lung disease (COPD). Intervention: Bronchial biopsy Intervention: Skin biopsy Intervention: Blood sample

Primary Outcome Measures

Name	Time	Method
functional bronchial epithelium from iPS?	Day 0 + culture (cross-sectional study)	Was a functional bronchial epithelium obtained from the patient's induced pluripotent stem cells from blood or fibroblasts? (yes/no)
functional bronchial epithelium from HBEC-ALI?	Day 0 + culture (cross-sectional study)	Was a functional bronchial epithelium obtained from the patient's bronchial biopsy: human bronchial epithelial cell culture on an air-liquid-interface? (yes/no)

Trial Locations

Locations (1)

Centre Hospitalier Universitaire de Montpellier; 🇫🇷 Montpellier, France