Novel pharmaco-exosomal immunotherapy for united airway diseases: PLGA-encapsulated, mesenchymal stem cell-derived exosomes with PPAR-γ agonist for allergic rhinitis and asthma

作者：Khawar Ali Shahzad, Zhao Wang, Boyu Cai, Xuran Li, Xiaohui Lv, Yanhong Wang, Fei Tan · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04624-8 · 被引用次数：9 · 研究领域：Allergic Rhinitis and Sensitization、Extracellular vesicles in disease、Asthma and respiratory diseases

BACKGROUND: The united airway diseases (UADs), exemplified by allergic rhinitis and asthma, cause significant morbidity. Although conventional pharmacotherapy provides symptomatic relief, recent evidence has indicated that cellular therapy, such as stem cell-derived exosomes, might offer therapeutic advantages throughout the entire respiratory tract. OBJECTIVES: The present study intends to demonstrate the effect and explore the mechanism of a novel pharmaco-exosomal immunotherapy, i.e., mesenchymal stem cells-derived exosomes (MSC-exo) supplemented with PPAR-γ agonists (Pioglitazone), which is locally delivered using PLGA nanoparticles (PLGA-exo-PIO) for the treatment of allergic airway diseases using male Balb/c mice. METHODS: The in vitro and in vivo therapeutic potential was observed using fluorescence imaging, RT-qPCR, ELISA, histopathology, flow cytometry, and bioinformatics analysis. RESULTS: Our results indicated that PLGA NPs exhibited prolonged retention and sustained release in the nasal cavity and lungs. In vitro, PLGA-exo-PIO treatment suppresses LPS-induced inflammation in nasal epithelial cells and mast cells. Using murine models of UADs, PLGA-exo-PIO therapy significantly improved the symptom score, reduced inflammatory cells (i.e., eosinophils and goblets) at tissue levels, and upregulated IFN-γ and IL-10 while downregulating histamine, IgE, LTC4, IL-4, and IL-17. In addition, flow cytometric analysis revealed elevated counts of Th1 cells, Tregs, and Bregs, a...