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

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...

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Main Authors: Sue Jean Mun, Shin Ae Kang, Hye-Kyung Park, Hak Sun Yu, Kyu-Sup Cho, Hwan-Jung Roh
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2021/6686625
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author Sue Jean Mun
Shin Ae Kang
Hye-Kyung Park
Hak Sun Yu
Kyu-Sup Cho
Hwan-Jung Roh
author_facet Sue Jean Mun
Shin Ae Kang
Hye-Kyung Park
Hak Sun Yu
Kyu-Sup Cho
Hwan-Jung Roh
author_sort Sue Jean Mun
collection DOAJ
description 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.
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spelling doaj-art-b85443e15a274f88ab34266920ee2fce2025-02-03T07:23:30ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/66866256686625Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of AsthmaSue Jean Mun0Shin Ae Kang1Hye-Kyung Park2Hak Sun Yu3Kyu-Sup Cho4Hwan-Jung Roh5Department of Otorhinolaryngology, Pusan National University Yangsan Hospital, Yangsan, Republic of KoreaDepartment of Parasitology and Tropical Medicine, Pusan National University School of Medicine, Yangsan, Republic of KoreaDepartment of Internal Medicine, Pusan National University Hospital, Busan, Republic of KoreaDepartment of Parasitology and Tropical Medicine, Pusan National University School of Medicine, Yangsan, Republic of KoreaDepartment of Otorhinolaryngology, Pusan National University Hospital, Busan, Republic of KoreaDepartment of Otorhinolaryngology, Pusan National University Yangsan Hospital, Yangsan, Republic of KoreaAsthma 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.http://dx.doi.org/10.1155/2021/6686625
spellingShingle Sue Jean Mun
Shin Ae Kang
Hye-Kyung Park
Hak Sun Yu
Kyu-Sup Cho
Hwan-Jung Roh
Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma
Stem Cells International
title Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma
title_full Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma
title_fullStr Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma
title_full_unstemmed Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma
title_short Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma
title_sort intranasally administered extracellular vesicles from adipose stem cells have immunomodulatory effects in a mouse model of asthma
url http://dx.doi.org/10.1155/2021/6686625
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