Epithelial stem cells from human small bronchi offer a potential for therapy of idiopathic pulmonary fibrosis.

Summary

Small bronchi basal cells in IPF exhibited a non-senescent phenotype with preserved proliferative/differentiative capacity comparable to controls. In a mouse fibrosis model, basal cell transplantation showed protective efficacy, and in three advanced IPF patients, autologous basal cell implantation via bronchoscopy improved lung volumes and small airway function.

Key Findings

• Small bronchi basal cells in IPF displayed a non-senescent phenotype with preserved proliferation and differentiation similar to healthy controls.
• Basal cell transplantation demonstrated protective efficacy and safety in a mouse pulmonary fibrosis model.
• Three advanced IPF patients receiving autologous basal cell transplantation showed improvements in lung volume and small airway function on spirometry and HRCT analyses.
• Single-cell RNA sequencing delineated airway epithelial senescence landscape and supported the preserved functionality of small-bronchi basal cells.

Clinical Implications

Bronchoscopic autologous basal cell implantation targeting small airways could complement current IPF care by improving small airway function. Careful patient selection, standardized cell manufacturing, and monitoring for long-term safety will be essential before broader adoption.

Limitations

• Human component is a small, uncontrolled case series (n=3) with short-term follow-up
• Generalizability and long-term safety/efficacy remain unproven

Future Directions

Conduct controlled phase 1/2 trials to establish dose, durability, and safety; refine cell manufacturing and delivery protocols; identify biomarkers for responder selection; and elucidate mechanisms of airway-epithelium-driven repair.