Shahzad Khawar Ali, Wang Zhao, Cai Boyu, Li Xuran, Lv Xiaohui, Wang Yanhong, Tan Fei
Department of ORL-HNS, Shanghai Fourth People's Hospital, and School of Medicine, Tongji University, Shanghai, China.
Plasma Medicine and Surgical Implants Center, Tongji University, Shanghai, China.
Stem Cell Res Ther. 2025 Sep 2;16(1):488. doi: 10.1186/s13287-025-04624-8.
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.
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.
The in vitro and in vivo therapeutic potential was observed using fluorescence imaging, RT-qPCR, ELISA, histopathology, flow cytometry, and bioinformatics analysis.
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, and reduced Th2 cells, eosinophils, and basophils in the blood and spleen of the treated mice. Finally, the data from bioinformatic analysis supported the therapeutic capabilities of fabricated PLGA-exo-PIO via regulation of multiple signaling pathways, such as the Notch cascade and NF-kB cascade.
For the first time, we used a PLGA-delivered, PIO-strengthened MSC-exo system (PLGA-exo-PIO) as a novel therapy to simultaneously manage AR and asthma as UADs.
以过敏性鼻炎和哮喘为代表的联合气道疾病（UADs）会导致严重的发病率。尽管传统药物治疗能缓解症状，但最近的证据表明，细胞疗法，如干细胞衍生的外泌体，可能在整个呼吸道提供治疗优势。
本研究旨在证明一种新型药物外泌体免疫疗法的效果并探索其机制，即间充质干细胞衍生的外泌体（MSC-exo）补充PPAR-γ激动剂（吡格列酮），使用聚乳酸-羟基乙酸共聚物纳米颗粒（PLGA）局部递送（PLGA-exo-PIO），用于治疗雄性Balb/c小鼠的过敏性气道疾病。
使用荧光成像、RT-qPCR、酶联免疫吸附测定、组织病理学、流式细胞术和生物信息学分析观察体外和体内治疗潜力。
我们的结果表明，PLGA纳米颗粒在鼻腔和肺部表现出延长的滞留和持续释放。在体外，PLGA-exo-PIO治疗可抑制脂多糖诱导的鼻上皮细胞和肥大细胞炎症。使用UADs小鼠模型，PLGA-exo-PIO疗法显著改善症状评分，降低组织水平的炎症细胞（即嗜酸性粒细胞和杯状细胞），上调干扰素-γ和白细胞介素-10，同时下调组胺、免疫球蛋白E、白三烯C4、白细胞介素-4和白细胞介素-17。此外，流式细胞术分析显示，治疗小鼠的血液和脾脏中辅助性T细胞1、调节性T细胞和调节性B细胞数量增加，辅助性T细胞2、嗜酸性粒细胞和嗜碱性粒细胞数量减少。最后，生物信息学分析数据支持了制备的PLGA-exo-PIO通过调节多种信号通路（如Notch级联和核因子κB级联）的治疗能力。
我们首次使用PLGA递送、PIO强化的MSC-exo系统（PLGA-exo-PIO）作为一种新型疗法，同时治疗作为UADs的过敏性鼻炎和哮喘。
