Idiopathic pulmonary fibrosis and lung epithelial tissue stem cell dysfunction

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease. Its pathological hallmark is abnormal scarring (fibrosis) of lung tissue, leading to irreversible loss of pulmonary function. Recent research proposes that IPF fundamentally represents a dysregulated wound healing response. This process initiates with injury to the respiratory epithelium, evolves through imperfect tissue repair, and culminates in pathological remodeling of lung tissue. Dysfunction of lung epithelial tissue stem cells plays a central role in this cascade. In IPF patients, adult lung tissue stem cells, including TP63⁺ KRT5⁺ airway basal cell (BC), AXIN2⁺ alveolar epithelial progenitor (AEP), and SCGB3A2⁺ respiratory airway secretory cell (RAS), exhibit significant impairment in stemness function. This manifests as increased senescence and aberrant differentiation, resulting in a imperfect wound healing response characterized by insufficient regenerative repair of the respiratory epithelium and active fibrotic repair. Intrapulmonary transplantation of tissue stem cells for IPF patients can achieve functional reconstitution of stem cells within the remodeled epithelium, leading to improvement in fibrotic lesions and lung function. Therapeutic strategies aimed at restoring the balance of lung tissue regeneration via stem cells hold promise for achieving disease control or even reversal in IPF.