Benefits of Epithelial Repair in COPD by Induced Pluripotent Stem Cells (iPS)
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Hospital, Montpellier
About this trial
The aim of this interventional, cross-sectional and pathophysiological experimental study is to evaluate the potential of a patient's induced pluripotent stem (iPS) cells, used prior to the re-differentiation stage, to enable ex vivo repair of the injured epithelium in patients with chronic obstructive pulmonary disease (COPD), smokers without COPD and non-smoking controls.
The main questions it aims to answer are:
* to evaluate the repair capacity of bronchial epithelium in COPD subjects, using a model of bronchial epithelium reconstituted in air/liquid interface culture and the iPS model. * epithelia repair capacities in normal or aberrant situations, as well as the time required for this repair, and to determine the involvement of grafted iPS cells in epithelia repair in cultured control subjects, smokers without COPD and COPD patients.
Researchers will compare 3 groups of participants (COPD patients, smokers without COPD and non-smokers without COPD) for epithelial repair efficacy between non-grafted ALI cultures and ALI cultures grafted with iPS cells, in order to assess their contribution to epithelial repair.
Participants will undergo a bronchial fibroscopy (for clinical indications) with two additional biopsies specific to the study.
This research could lead to breakthroughs in cell-based therapies for COPD, with long-term implications for epigenetic treatments and in vivo applications.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participants with a bronchoscopy indication determined by a pulmonologist (e.g., follow-up exploration, nodule investigation, hemoptysis, cough, sputum production, recurrent bronchitis, or differential diagnosis).
Current or former smokers (≥10 pack-years).
Diagnosed with COPD: FEV1/FVC < 0.7 (confirmed by spirometry available in the medical file within the past year).
Current or former smokers (≥10 pack-years).
Disqualifiers
Participant with extensive neoplastic disease.
Participant with another progressive pulmonary condition (e.g., asthma, tuberculosis, interstitial lung disease, active or recent pulmonary infection).
Participant consuming illicit drugs or alcohol.
Individual deprived of liberty (by judicial or administrative decision, or under involuntary hospitalization).
Trial design
Design model
Parallel
Treatments tested in this trial
bronchial fibroscopy
Procedure/Surgery2 bronchial biopsies will be taken during bronchial fibroscopy
Treatment groups
50 Participants
are divided into 3 treatment groupsGroup A: smoker with COPDExperimental treatment 1 intervention
Group B: smoker without COPDActive comparator 1 intervention
Group C: healthy non-smoking subjectActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
The main objective is to evaluate the repair capacity of the bronchial epithelium of COPD subjects using the reconstituted bronchial epithelium model in air/liquid interface culture and the iPS model.
Percentage of repair at 24 hours post-lesion of ALI cultures vs. the same ALI cultures "grafted with iPS". This percentage will be determined by the surface area of the culture reconstructed after scratching divided by the surface area initially scratched.
Time frame
Day 1Secondary outcomes
1
comparison of % repair of post-scratch cultures in the presence or absence of IPS between the 3 groups
Calculation of the percentage of repair at 48 hours, 72 hours and at 7 days post-scratch. This percentage will be determined by the surface area of the culture rebuilt after scratching divided by the surface area initially scratched.
Time frame
Day 2, Day 3 and day 72
Comparison of transepithelial electrical resistances between groups
Verification of the integrity of the bronchial epithelium obtained by measuring the transepithelial electrical resistance. (expressed as Ω/cm2 at each time point).
Time frame
Day 2, Day 3 and day 73
Determining the proportion of GFP-tagged iPS cells vs. native cells in lesion repair:
Cell density measurements (% GFP cells/total cells) by microscopy at each time point
Time frame
Day 2, Day 3 and day 74
Phenotyping of native and GFP+ iPS populations by immunofluorescent labeling of different cell types (ciliated cells, mucus cells, club cells, basal cells)
immunofluorescence will be used to assess the density of basal, club, ciliated and caliciform cells; the release of key proinflammatory cytokines classically implicated in COPD will be assayed in the supernatant of these cultures.
Time frame
Day 2, Day 3 and day 7Sponsors and contacts
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Source ClinicalTrials.gov