Cell therapy for asthma: mechanistic basis, translational challenges, and future directions

Asthma is a chronic airway disease marked by substantial clinical, inflammatory, and structural heterogeneity. Although inhaled therapies and targeted biologics have improved disease control in many patients, persistent inflammation, treatment resistance, and airway remodeling remain major unmet needs. Cell-based and cell-derived therapies have therefore attracted increasing interest because they may act on multiple pathological processes, including immune regulation, epithelial repair, and tissue remodeling. This review summarizes current cell therapy strategies for asthma, with particular emphasis on mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs), and discusses their mechanisms of action, translational barriers, and future development. Current evidence is strongest for MSCs and MSC-EVs. These platforms may attenuate airway inflammation by modulating epithelial alarmin release, dendritic cell and macrophage activation, type 2 responses, Th17/Treg imbalance, and remodeling-related pathways. Immune tolerance-oriented platforms, including regulatory T cells, regulatory B cells, and tolerogenic dendritic cells, together with engineered cell strategies, further broaden the therapeutic scope but remain largely exploratory in asthma. Despite encouraging preclinical findings, translation is constrained by the limited representativeness of current disease models, product heterogeneity, insufficient manufacturing and potency standards, uncertainty around delivery routes and treatment regimens, and limited long-term clinical evidence. Future progress will require closer alignment among disease endotypes, model selection, therapeutic platforms, delivery strategies, and outcome measures. Rather than treating cell therapy as a broadly applicable anti-inflammatory intervention, future studies should define the disease settings and patient subgroups in which each platform is most likely to provide reproducible and clinically meaningful benefit.