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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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Published in: | Stem cells international 2021-07, Vol.2021, p.6686625-11 |
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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 |
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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.</description><identifier>ISSN: 1687-966X</identifier><identifier>ISSN: 1687-9678</identifier><identifier>EISSN: 1687-9678</identifier><identifier>DOI: 10.1155/2021/6686625</identifier><identifier>PMID: 34899920</identifier><language>eng</language><publisher>United States: Hindawi</publisher><subject>Albumin ; Allergens ; Allergic diseases ; Allergies ; Analysis ; Asthma ; Body fat ; Bronchus ; Cell culture ; Cytokines ; Eosinophils ; Extracellular vesicles ; Immunoglobulin G ; Immunoglobulins ; Immunomodulation ; Inflammation ; Interleukins ; Lavage ; Leukocytes (eosinophilic) ; Lungs ; Lymph nodes ; Lymphatic system ; Lymphocytes ; Lymphocytes T ; Mice ; Ovalbumin ; Respiratory tract diseases ; Stem cell transplantation ; Stem cells ; T cells ; Vesicles</subject><ispartof>Stem cells international, 2021-07, Vol.2021, p.6686625-11</ispartof><rights>Copyright © 2021 Sue Jean Mun et al.</rights><rights>COPYRIGHT 2021 John Wiley & Sons, Inc.</rights><rights>Copyright © 2021 Sue Jean Mun et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2021 Sue Jean Mun et al. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c612t-fd0e1f0d90b0a40c212aa0ffe684c97cf1fad7ea4558cbb161e0bd21dcce55bb3</citedby><cites>FETCH-LOGICAL-c612t-fd0e1f0d90b0a40c212aa0ffe684c97cf1fad7ea4558cbb161e0bd21dcce55bb3</cites><orcidid>0000-0002-3055-8713 ; 0000-0002-4381-6996 ; 0000-0003-4486-7178</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2609153323/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2609153323?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34899920$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Abdelalim, Essam M.</contributor><contributor>Essam M Abdelalim</contributor><creatorcontrib>Mun, Sue Jean</creatorcontrib><creatorcontrib>Kang, Shin Ae</creatorcontrib><creatorcontrib>Park, Hye-Kyung</creatorcontrib><creatorcontrib>Yu, Hak Sun</creatorcontrib><creatorcontrib>Cho, Kyu-Sup</creatorcontrib><creatorcontrib>Roh, Hwan-Jung</creatorcontrib><title>Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma</title><title>Stem cells international</title><addtitle>Stem Cells Int</addtitle><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.</description><subject>Albumin</subject><subject>Allergens</subject><subject>Allergic diseases</subject><subject>Allergies</subject><subject>Analysis</subject><subject>Asthma</subject><subject>Body fat</subject><subject>Bronchus</subject><subject>Cell culture</subject><subject>Cytokines</subject><subject>Eosinophils</subject><subject>Extracellular vesicles</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulins</subject><subject>Immunomodulation</subject><subject>Inflammation</subject><subject>Interleukins</subject><subject>Lavage</subject><subject>Leukocytes (eosinophilic)</subject><subject>Lungs</subject><subject>Lymph nodes</subject><subject>Lymphatic system</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Ovalbumin</subject><subject>Respiratory tract diseases</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>T cells</subject><subject>Vesicles</subject><issn>1687-966X</issn><issn>1687-9678</issn><issn>1687-9678</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9ks2LEzEYhwdR3KXuzbMEBBG0u0lmJjNzEUqpbmEXD37gLWSSN23KJKnJzGqP_udmbK1bEZNDQvK8D-SXN8ueEnxJSFleUUzJFWM1Y7R8kJ0TVlfThlX1w-OefTnLLmLc4DTyBheYPs7O8qJumobi8-zH0vVBOBFF1-3QTFnjTOwhgEKL7-lGQtcNnQjoM0QjO4hIB28TaLY-AvrQg0XzxER0Le4ALa0dnLdepZrehx1aaA2yj8g4JNCtH1LNrVfQIa_RLPZrK55kj7ToIlwc1kn26e3i4_x6evP-3XI-u5lKRmg_1QoD0Vg1uMWiwJISKgROdlYXsqmkJlqoCkRRlrVsW8II4FZRoqSEsmzbfJIt917lxYZvg7Ei7LgXhv868GHFRejHN_K2LosiB1IKWhW6rkWbF5SxFBgA1RKS683etR1aC0rCGGJ3Ij29cWbNV_6Op48qRvcke3kQBP91gNhza-KYtXCQQuKUEYyrOmcj-vwvdOOH4FJUicINKfOc5n-olUgPME778fNGKZ-xhjVVkWSJuvwHlaYCa6R3oE06Pyl4ca9gDaLr19F3Q2-8i6fg6z0og48xgD6GQTAfW5WPrcoPrZrwZ_cDPMK_GzMBr_bA2jglvpn_634Cxqvw7Q</recordid><startdate>20210731</startdate><enddate>20210731</enddate><creator>Mun, Sue Jean</creator><creator>Kang, Shin Ae</creator><creator>Park, Hye-Kyung</creator><creator>Yu, Hak Sun</creator><creator>Cho, Kyu-Sup</creator><creator>Roh, Hwan-Jung</creator><general>Hindawi</general><general>John Wiley & Sons, Inc</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QO</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M2O</scope><scope>MBDVC</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3055-8713</orcidid><orcidid>https://orcid.org/0000-0002-4381-6996</orcidid><orcidid>https://orcid.org/0000-0003-4486-7178</orcidid></search><sort><creationdate>20210731</creationdate><title>Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma</title><author>Mun, Sue Jean ; 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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.</abstract><cop>United States</cop><pub>Hindawi</pub><pmid>34899920</pmid><doi>10.1155/2021/6686625</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3055-8713</orcidid><orcidid>https://orcid.org/0000-0002-4381-6996</orcidid><orcidid>https://orcid.org/0000-0003-4486-7178</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Albumin Allergens Allergic diseases Allergies Analysis Asthma Body fat Bronchus Cell culture Cytokines Eosinophils Extracellular vesicles Immunoglobulin G Immunoglobulins Immunomodulation Inflammation Interleukins Lavage Leukocytes (eosinophilic) Lungs Lymph nodes Lymphatic system Lymphocytes Lymphocytes T Mice Ovalbumin Respiratory tract diseases Stem cell transplantation Stem cells T cells Vesicles |
title | Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma |
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