Stem Cell Trial: iPSCs for Repairing Airway Damage in COPD
The study will test whether induced pluripotent stem cells can help repair airway damage in people with COPD.
Researchers at University Hospital, Montpellier (France) are preparing to begin an experimental study evaluating the potential of induced pluripotent stem cells (iPS cells) to repair airway epithelial damage in people with chronic obstructive pulmonary disease (COPD). The trial (RepCOPDiPS) is set to start in early 2025 at the University Hospital of Montpellier and is led by principal investigator Dr. Mathilde Volpato.
COPD is a progressive respiratory disease that leads to persistent airway inflammation, loss of functional lung tissue, and impaired repair of the bronchial epithelium. Current treatments manage symptoms but do not address the underlying epithelial dysfunction. The study team reports that regenerative cell therapy may offer a new approach to restore healthy airway lining and potentially modify disease progression. The trial will enroll an estimated 50 adults scheduled for bronchial fibroscopy for clinical reasons.
Participants will be assigned to one of three groups:
- Smokers with COPD
- Smokers without COPD
- Healthy non-smoking controls
Each participant will undergo two additional bronchial biopsies. Researchers will use these tissue samples to grow airway epithelial cultures in the laboratory, both with and without the addition of iPS cells. The iPS cells will be used prior to their full differentiation to assess their repair potential when grafted onto injured epithelial cultures. The primary objective is to evaluate the capacity of iPS cells to promote repair of the bronchial epithelial layer in an ex vivo air-liquid interface (ALI) model, by comparing the percentage of repaired surface area at 24 hours post-lesion in cultures grafted with iPS cells versus those without.
Secondary objectives include:
- Comparing repair rates at later time points (48 hours, 72 hours, and 7 days)
- Measuring the integrity of the epithelial barrier via transepithelial electrical resistance
- Tracking the proportion of GFP-labeled iPS cells versus native cells involved in repair
- Immunofluorescent phenotyping of various airway cell types (ciliated, mucus, club, basal cells)
- Transcriptomic profiling to compare gene expression between native and iPS-derived cells, and between ungrafted/grafted cultures
- Assessing restoration of the ciliated cell/caliciform cell ratio—of particular interest, as the investigators previously reported a deficit in club cells destined to become ciliated cells in COPD
The researchers note that advances in iPS technology allow for nearly unlimited production of patient-matched or universal donor pluripotent cells capable of forming airway epithelial types. Their preclinical work has shown promising results in differentiating iPS cells into bronchial epithelial cells that replicate key properties of healthy airway lining. If successful, the team suggests this approach could pave the way for future epigenetic or cell-based therapies targeting epithelial dysfunction in COPD. Study completion is expected around January 2027.
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