Intranasal delivery of MSCs-Exo reduces AR inflammation
To further understand the effects of MSCs-Exo on AR, the levels of different inflammation-related indicators were measured. As shown in Figure 2C, sections of the control group revealed normal nasal cavity mucosa. In the AR group, we observed more infiltrating eosinophils and lymphocytes, glandular secretion, and mucosal swelling (Figure 2D). After MSCs-Exo treatment, there were significantly fewer infiltrating cells and less glandular secretion and mucosal swelling in the nasal mucosa (Figure 2E). Additionally, the quantification of eosinophils (Figure 2F) suggested that MSCs-Exo have a therapeutic effect on AR mice. The spleen index, which also reflects the inflammatory status, demonstrated similar differences between the three groups (Figure 3A). Spleen sections from different groups are shown in Figure 3B–D. We observed apparent splenic sinus edema, splenic capsule incrassation, and vasodilation in the AR group (Figure 3C), and MSCs-Exo administration reduced inflammation.
The cytokine levels in the spleen, including Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13, and TGF-β), a Th1 cytokine (IFN-γ), a Th17 cytokine (IL-17), an eosinophil chemoattractant (CCL-11)20, and an adhesion receptor (ICAM-1)21, were analyzed by RT-PCR at 24 h after the last treatment. As shown in Figure 4A, IL-4, IL-5, IL-6, IL-13, CCL-11, and ICAM-1 levels were significantly decreased in the MSCs-Exo group compared to the AR group. While there were no differences in IL-17 and TGF-β levels, IL-10 and IFN-γ levels were obviously enhanced in the MSCs-Exo group compared to the AR group. The serum concentrations of histamine, OVA-IgE, IgE, IgG1, and IgG2a, and the concentrations of histamine, OVA-IgE, and IgG1 in bronchoalveolar lavage fluid (BALF), were measured by ELISA. The MSCs-Exo mice expressed low levels of OVA-IgE, IgE, and IgG1, but not IgG2a (Figure 4B and C). These results verify our hypothesis that intranasal delivery of MSCs-Exo could inhibit allergic airway inflammation and regulate the balance of Th1/Th2 in OVA-sensitized mice.