Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma

Abstract

Asthma is a chronic eosinophilic airway disease characterized by type 2 helper T cell-driven inflammation. Adipose stem cells (ASCs) and the ASC culture supernatant are known to improve allergic airway inflammation; however, the immunomodulatory effects of ASC-derived extracellular vesicles (EVs) on allergic airway diseases remain unclear. Thus, we assessed the effects of ASC-derived EVs on allergic airway inflammation in a mouse model of asthma. EVs were isolated from the culture supernatant of murine ASCs and characterized. Six-week-old female C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. Before the OVA challenge, 10 μg/50 μl of ASC-derived EVs was administered intranasally to the experimental group. ASC-derived EVs significantly attenuated airway hyperresponsiveness (AHR) in asthmatic mice ( p = 0.023 ). ASC-derived EVs resulted in a remarkable reduction of the total number of inflammatory cells ( p = 0.005 ) and eosinophils ( p = 0.023 ) in the bronchoalveolar lavage fluid (BALF), the degree of eosinophilic lung inflammation ( p < 0.001 ), and the serum total and OVA-specific immunoglobulin (Ig)E ( p = 0.048 and p = 0.001 ) and total IgG1 ( p < 0.001 ). Interleukin- (IL-) 4 was significantly inhibited with ASC-derived EV pretreatment in the BALF and lung draining lymph nodes (LLNs) ( p = 0.040 and p = 0.011 ). Furthermore, ASC-derived EV administration resulted in a significant increase of the regulatory T cell (Treg) populations in LLNs. ASC-derived EVs alleviated AHR and allergic airway inflammation caused by the induction of Treg expansion in a mouse model of asthma. There seems to be a role for ASC-derived EVs as a modifier in allergic airway disease.

Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases

“…Moreover, hypoxic-EVs were generally more potent in suppressing airway inflammation, preventing airway remodeling, and decreasing the expression of pro-fibrogenic markers [ 160 ]. Additionally, in OVA-mice, it was also found that EVs from MSCs in adipose tissue helped reduce allergic airway inflammation and airway hyperresponsiveness caused by the activation of regulatory T cells to expansion [ 161 ]. Despite the encouraging results, to identify the EV components responsible for the suppression of allergic airway inflammation in asthmatic mice, additional investigations are required.…”

Mesenchymal Stem Cell-derived Exosome: An Interesting Nanocarrier to Improve Allergen-specific Intranasal Immunotherapy

“…In this case, Mun et al, reported that intranasal MSC-derived exosomes significantly reduced airway hyper-responsiveness and bronchial alveolar fluid eosinophil count and decreased the levels of total and specific IgE and IL-4 secretion, while Treg populations were dramatically increased. 38 Furthermore, Ren et al, reported that intranasal MSCderived exosomes efficiently ameliorate allergic airway inflammation through increased IL-10 production. 13 Another important aspect is the loading of allergens into these nanoscale vesicles.…”

SCGB1C1 Plays a Critical Role in Suppression of Allergic Airway Inflammation through the Induction of Regulatory T Cell Expansion

“…MSCs-derived EVs have been reported to be promising candidates for the treatment of allergic airway diseases due to their immunomodulatory properties [ 10 , 22 ]. Several studies have shown that ASC-derived EV treatment significantly improved allergic airway inflammation through the suppression of Th2 cytokine production and induction of Treg expansion [ 15 , 18 ]. Furthermore, ASC-derived EVs have been shown to reduce AHR and improve lung function in asthmatic mice [ 15 ].…”

“…The MSC secretome or MSC-derived extracellular vesicles (EVs) were as effective as MSCs themselves in improving allergic airway diseases [ 10 , 11 , 12 , 13 , 14 , 15 ]. The EVs of ASCs ameliorated Th2-mediated inflammation through the activation of dendritic cells and the induction of M2 macrophage polarization [ 16 , 17 , 18 ].…”