Abstract
Progressive pulmonary fibrosis (PPF) is a clinical phenotype characterized by worsening fibrosis, declining lung function, and progressive respiratory symptoms despite appropriate treatment of the underlying interstitial lung disease (ILD). It may develop in several fibrotic ILDs other than idiopathic pulmonary fibrosis, including fibrotic hypersensitivity pneumonitis, nonspecific interstitial pneumonia, and connective tissue disease-associated ILD. PPF is associated with irreversible structural lung damage, reduced quality of life, and increased mortality. Despite the development of standard antifibrotic agents, specifically nintedanib and pirfenidone, therapeutic failure and disease progression remain common outcomes. Consequently, mesenchymal stromal cells (MSCs) represent a promising therapeutic approach due to their immunomodulatory, anti-inflammatory, and antifibrotic properties. This review evaluates the rationale for MSC-based therapy in fibrotic lung disease, summarizes available preclinical and clinical evidence, and discusses the limitations, safety considerations, and research priorities that must be addressed before clinical application can be established.