Recent progress on airway basal stem cells in chronic respiratory diseases

Abstract

Airway basal stem cells (ABSCs), as tissue-resident adult stem cells within the pulmonary epithelium, possess potent self-renewal and multilineage differentiation capacities. They not only serve as the cornerstone for maintaining airway epithelial homeostasis and mediating injury repair, but their dysfunction also acts as a critical factor driving the initiation and progression of chronic respiratory diseases (CRDs). The global incidence of CRDs continues to rise each year, whereas their clinical diagnosis and treatment remain limited by significant bottlenecks. Therefore, in-depth exploration of the biological characteristics and pathological alterations of ABSCs is of great significance for overcoming these clinical dilemmas. This review systematically elaborates on the biological features and fate regulatory mechanisms of ABSCs, and further elucidates the molecular mechanisms underlying the pathological alterations of ABSCs in multiple CRDs. In addition, we summarize the translational prospects of ABSCs in disease modeling, precision medicine, and cell-based transplantation therapy. While recent studies have yielded substantial progress in ABSCs’ basic research, multiple critical barriers still impede their clinical translation. These major obstacles include poorly defined cellular heterogeneity landscapes, intricate intercellular crosstalk within diseased airway niches, and the absence of robust, scalable systems for clinical-grade ABSCs preparation. Resolving these key research gaps is essential to bridge the translational divide between bench research and clinical application. Promoting the clinical translation of ABSCs for CRDs is of great significance. ABSCs can not only play a key role in the early diagnosis and prevention of CRDs, but also hold the potential to transform therapeutic paradigms from symptomatic relief toward fundamental epithelial repair, thereby providing innovative diagnostic and therapeutic strategies for CRDs and other chronic diseases associated with epithelial dysfunction.