Airway basal stem cell therapy for lung diseases: an emerging regenerative medicine strategy

Chronic pulmonary diseases pose a prominent health threat globally owing to their intricate pathogenesis and lack of effective reversal therapies. Nowadays, lung transplantation stands out as a feasible treatment option for patients with end-stage lung disease. Unfortunately, the use of this this option is limited by donor organ shortage and severe immunological rejection reactions. Recently, airway basal stem cells (BSCs) have emerged as a novel therapeutic strategy in pulmonary regenerative medicine because of their substantial potential in repairing lung structure and function. Airway BSCs, which are strongly capable of self-renewal and multi-lineage differentiation, can effectively attenuate airway epithelial injury caused by environmental factors or genetic disorders, such as cystic fibrosis. This review comprehensively explores the efficacy and action mechanisms of airway BSCs across various lung disease models and describes potential strategies for inducing pluripotent stem cells to differentiate into pulmonary epithelial lineages on the basis of the original research findings. Additionally, the review also discusses the technical and biological challenges in translating these research findings into clinical applications and offers prospective views on future research directions, therefore broadening the landscape of pulmonary regenerative medicine.