■过敏性鼻炎(AR)是鼻粘膜的上呼吸道炎性疾病。常规治疗如症状性药物疗法和变应原特异性免疫疗法具有相当的局限性和缺点。作为一种具有再生潜力和免疫调节作用的新兴疗法,间充质干细胞来源的外泌体(MSC-Exos)最近已被用于治疗各种炎症和自身免疫性疾病。
■为了实现持续和受保护的MSC-Exos释放,用于鼻内给药,我们使用机械双重乳液制备了聚(乳酸-乙醇酸共聚物)(PLGA)微米和纳米颗粒封装的MSC-Exos(PLGA-Exos)用于AR的局部治疗。临床前体内成像,ELISA,qPCR,流式细胞术,免疫组织化学染色,和多组学测序用于表型和机制评估PLGA-Exos在体外和体内的治疗效果。
■结果表明,我们的PLGA平台可以持续有效地封装和释放外泌体。在蛋白质水平,PLGA-Exos治疗上调IL-2、IL-10和IFN-γ,在卵清蛋白(OVA)诱导的AR小鼠中下调IL-4,IL-17和抗原特异性IgE。在细胞水平,外泌体治疗减少了Th2细胞,增加了Tregs,重建Th1/Th2平衡。在组织层面,PLGA-Exos显着减弱了免疫细胞的浸润(例如,嗜酸性粒细胞和杯状细胞)在鼻粘膜中。最后,多组学分析发现了几个信号级联,例如,过氧化物酶体增殖物激活受体(PPAR)途径和糖酵解途径,这可能在机械上支持PLGA-Exos的免疫调节作用。
■第一次,我们提出了一种用于干细胞来源外泌体的生物材料促进的局部递送系统,作为AR治疗的一种新颖且有前景的策略.
UNASSIGNED: Allergic rhinitis (AR) is an upper airway inflammatory disease of the nasal mucosa. Conventional treatments such as symptomatic pharmacotherapy and allergen-specific immunotherapy have considerable limitations and drawbacks. As an emerging therapy with regenerative potential and immunomodulatory effect, mesenchymal stem cell-derived exosomes (MSC-Exos) have recently been trialed for the treatment of various inflammatory and autoimmune diseases.
UNASSIGNED: In order to achieve sustained and protected release of MSC-Exos for intranasal administration, we fabricated Poly(lactic-co-glycolic acid) (PLGA) micro and nanoparticles-encapsulated MSC-Exos (PLGA-Exos) using mechanical double emulsion for local treatment of AR. Preclinical in vivo imaging, ELISA, qPCR, flow cytometry, immunohistochemical staining, and multiomics sequencing were used for phenotypic and mechanistic evaluation of the therapeutic effect of PLGA-Exos in vitro and in vivo.
UNASSIGNED: The results showed that our PLGA platform could efficiently encapsulate and release the exosomes in a sustained manner. At protein level, PLGA-Exos treatment upregulated IL-2, IL-10 and IFN-γ, and downregulated IL-4, IL-17 and antigen-specific IgE in ovalbumin (OVA)-induced AR mice. At cellular level, exosomes treatment reduced Th2 cells, increased Tregs, and reestablished Th1/Th2 balance. At tissue level, PLGA-Exos significantly attenuated the infiltration of immune cells (e.g., eosinophils and goblet cells) in nasal mucosa. Finally, multiomics analysis discovered several signaling cascades, e.g., peroxisome proliferator-activated receptor (PPAR) pathway and glycolysis pathway, that might mechanistically support the immunomodulatory effect of PLGA-Exos.
UNASSIGNED: For the first time, we present a biomaterial-facilitated local delivery system for stem cell-derived exosomes as a novel and promising strategy for AR treatment.