Abstract

Chronic Obstructive Pulmonary Disease (COPD) represents a significant global health burden characterized by progressive airflow limitation and persistent respiratory symptoms. Despite current pharmacological interventions, disease modification remains elusive. Mesenchymal stem cell (MSC) therapy has emerged as a promising regenerative approach targeting the core inflammatory and destructive processes underlying COPD pathogenesis. This comprehensive review examines the mechanistic basis of MSC therapy, synthesizes clinical evidence from 25 registered trials and 9 published studies, and provides evidence-based recommendations for clinical translation. MSCs exert multifaceted therapeutic effects primarily through paracrine-mediated immunomodulation, anti-fibrotic activity, and tissue repair promotion. Clinical data demonstrate consistent safety profiles and significant improvements in symptom burden and exacerbation frequency, though without substantial changes in FEV1. Optimal protocols suggest intravenous administration of 100 million umbilical cord-derived MSCs in two doses over three months. While Phase III trials are warranted, MSC therapy offers a paradigm shift toward disease modification in COPD management.