IL-37 overexpression enhances the therapeutic effect of endometrial regenerative cells in concanavalin A-induced hepatitis
Mesenchymal stromal cells and immunosuppressive factor IL-37 can both suppress concanavalin A (Con A)-induced hepatitis in mice. Endometrial regenerative cells (ERCs), novel types of mesenchymal-like stromal cells, possess powerful immunomodulatory effects and are effective in treating various disea...
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| Veröffentlicht in: | Cytotherapy (Oxford, England) England), 2021-07, Vol.23 (7), p.617-626 |
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| container_title | Cytotherapy (Oxford, England) |
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| creator | Li, Guangming Kong, Dejun Qin, Yafei Wang, Hongda Hu, Yonghao Zhao, Yiming Hao, Jingpeng Qin, Hong Yu, Dingding Zhu, Yanglin Sun, Chenglu Wang, Hao |
| description | Mesenchymal stromal cells and immunosuppressive factor IL-37 can both suppress concanavalin A (Con A)-induced hepatitis in mice. Endometrial regenerative cells (ERCs), novel types of mesenchymal-like stromal cells, possess powerful immunomodulatory effects and are effective in treating various diseases. The aim of this study was to explore the effects of ERCs in suppressing Con A-induced hepatitis and determine whether IL-37 overexpression could enhance the therapeutic effect of ERCs in this process.
ERCs were extracted from the menstrual blood of healthy female volunteer donors. The IL-37 gene was transferred into ERCs, and the expression of IL-37 in cells was detected by western blot and enzyme-linked immunosorbent assay. Hepatitis was induced by Con A in C57BL/6 mice that were randomly divided into groups treated with phosphate-buffered saline, ERCs, IL-37 or ERCs transfected with the IL-37 gene (IL-37-ERCs). Cell tracking, liver function, histopathological and immunohistological changes, immune cell proportions and levels of cytokines were measured 24 h after Con A administration.
Compared with ERC or IL-37 treatment, IL-37-ERCs further reduced levels of liver enzymes (alanine aminotransferase and aspartate aminotransferase) and improved histopathological changes in the liver. In addition, IL-37-ERC treatment further reduced the proportions of M1 macrophages and CD4+ T cells and increased the proportion of regulatory T cells. Moreover, IL-37-ERC treatment resulted in lower levels of IL-12 and interferon gamma, and higher level of transforming growth factor beta.
The results of this study suggest that ERCs can effectively alleviate Con A-induced hepatitis. Furthermore, IL-37 overexpression can significantly enhance the therapeutic efficacy of ERCs by augmenting the immunomodulatory and anti-inflammatory properties of ERCs. This study may provide a promising strategy for treatment of T-cell-dependent hepatitis. |
| doi_str_mv | 10.1016/j.jcyt.2020.12.006 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_33593687</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1465324920309865</els_id><sourcerecordid>2528507697</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-9f555b456ecb1de606505d7e31c59b86e8feaaf7f2e50825087e30b79862a6bc3</originalsourceid><addsrcrecordid>eNqNkUtr3DAURk1paNK0f6CLomWheCLLo4ehmzD0ERjoJlkLWb7qaPBIriRPmv76XjPTLEsXF73Od5GOqupdQ1cNbcTNfrW3T2XFKMMNtqJUvKiumrWUNeNCvFzmgtctW3eX1euc9xRBpfir6rJtedcKJa-q33fbupUkHiHBrylBzj4GAmFngoVMyg6WSmaCuXhLwDmwhUSHyBAPUJI3I0nwAwJCxR-BWBjHTHwgNgZrgjmaERe3tQ_DbGEgO5gQLD6_qS6cGTO8PY_X1cOXz_ebb_X2-9e7ze22ti0Xpe4c57xfcwG2bwYQVHDKBwltY3nXKwHKgTFOOgacKoaFZ7SXnRLMiN6219WHU98pxZ8z5KIPPi-3NAHinDXjTHEqRScRZSfUpphzAqen5A8mPemG6sW53uvFuV6c64ZpdI6h9-f-c3-A4TnyVzIC6gQ8Qh9dth7Q7TNGsYdoFVUNzqjc-IJ6YtjEORSMfvz_KNKfTjSgzqOHpM-JwSf8Nj1E_6-H_AGe1bWY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2528507697</pqid></control><display><type>article</type><title>IL-37 overexpression enhances the therapeutic effect of endometrial regenerative cells in concanavalin A-induced hepatitis</title><source>MEDLINE</source><source>Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><source>Alma/SFX Local Collection</source><creator>Li, Guangming ; Kong, Dejun ; Qin, Yafei ; Wang, Hongda ; Hu, Yonghao ; Zhao, Yiming ; Hao, Jingpeng ; Qin, Hong ; Yu, Dingding ; Zhu, Yanglin ; Sun, Chenglu ; Wang, Hao</creator><creatorcontrib>Li, Guangming ; Kong, Dejun ; Qin, Yafei ; Wang, Hongda ; Hu, Yonghao ; Zhao, Yiming ; Hao, Jingpeng ; Qin, Hong ; Yu, Dingding ; Zhu, Yanglin ; Sun, Chenglu ; Wang, Hao</creatorcontrib><description>Mesenchymal stromal cells and immunosuppressive factor IL-37 can both suppress concanavalin A (Con A)-induced hepatitis in mice. Endometrial regenerative cells (ERCs), novel types of mesenchymal-like stromal cells, possess powerful immunomodulatory effects and are effective in treating various diseases. The aim of this study was to explore the effects of ERCs in suppressing Con A-induced hepatitis and determine whether IL-37 overexpression could enhance the therapeutic effect of ERCs in this process.
ERCs were extracted from the menstrual blood of healthy female volunteer donors. The IL-37 gene was transferred into ERCs, and the expression of IL-37 in cells was detected by western blot and enzyme-linked immunosorbent assay. Hepatitis was induced by Con A in C57BL/6 mice that were randomly divided into groups treated with phosphate-buffered saline, ERCs, IL-37 or ERCs transfected with the IL-37 gene (IL-37-ERCs). Cell tracking, liver function, histopathological and immunohistological changes, immune cell proportions and levels of cytokines were measured 24 h after Con A administration.
Compared with ERC or IL-37 treatment, IL-37-ERCs further reduced levels of liver enzymes (alanine aminotransferase and aspartate aminotransferase) and improved histopathological changes in the liver. In addition, IL-37-ERC treatment further reduced the proportions of M1 macrophages and CD4+ T cells and increased the proportion of regulatory T cells. Moreover, IL-37-ERC treatment resulted in lower levels of IL-12 and interferon gamma, and higher level of transforming growth factor beta.
The results of this study suggest that ERCs can effectively alleviate Con A-induced hepatitis. Furthermore, IL-37 overexpression can significantly enhance the therapeutic efficacy of ERCs by augmenting the immunomodulatory and anti-inflammatory properties of ERCs. This study may provide a promising strategy for treatment of T-cell-dependent hepatitis.</description><identifier>ISSN: 1465-3249</identifier><identifier>EISSN: 1477-2566</identifier><identifier>DOI: 10.1016/j.jcyt.2020.12.006</identifier><identifier>PMID: 33593687</identifier><language>eng</language><publisher>OXFORD: Elsevier Inc</publisher><subject><![CDATA[Animals ; Biotechnology & Applied Microbiology ; Cell & Tissue Engineering ; Cell Biology ; Concanavalin A ; concanavalin A-induced hepatitis ; Cytokines ; endometrial regenerative cells ; Endometrium ; Female ; Hematology ; Hepatitis ; IL-37 ; Life Sciences & Biomedicine ; Liver ; Medicine, Research & Experimental ; Mice ; Mice, Inbred C57BL ; Research & Experimental Medicine ; Science & Technology ; T-cell-dependent liver injury]]></subject><ispartof>Cytotherapy (Oxford, England), 2021-07, Vol.23 (7), p.617-626</ispartof><rights>2021 International Society for Cell & Gene Therapy</rights><rights>Copyright © 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>9</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000663808100007</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c356t-9f555b456ecb1de606505d7e31c59b86e8feaaf7f2e50825087e30b79862a6bc3</citedby><cites>FETCH-LOGICAL-c356t-9f555b456ecb1de606505d7e31c59b86e8feaaf7f2e50825087e30b79862a6bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932,39265</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33593687$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Guangming</creatorcontrib><creatorcontrib>Kong, Dejun</creatorcontrib><creatorcontrib>Qin, Yafei</creatorcontrib><creatorcontrib>Wang, Hongda</creatorcontrib><creatorcontrib>Hu, Yonghao</creatorcontrib><creatorcontrib>Zhao, Yiming</creatorcontrib><creatorcontrib>Hao, Jingpeng</creatorcontrib><creatorcontrib>Qin, Hong</creatorcontrib><creatorcontrib>Yu, Dingding</creatorcontrib><creatorcontrib>Zhu, Yanglin</creatorcontrib><creatorcontrib>Sun, Chenglu</creatorcontrib><creatorcontrib>Wang, Hao</creatorcontrib><title>IL-37 overexpression enhances the therapeutic effect of endometrial regenerative cells in concanavalin A-induced hepatitis</title><title>Cytotherapy (Oxford, England)</title><addtitle>CYTOTHERAPY</addtitle><addtitle>Cytotherapy</addtitle><description>Mesenchymal stromal cells and immunosuppressive factor IL-37 can both suppress concanavalin A (Con A)-induced hepatitis in mice. Endometrial regenerative cells (ERCs), novel types of mesenchymal-like stromal cells, possess powerful immunomodulatory effects and are effective in treating various diseases. The aim of this study was to explore the effects of ERCs in suppressing Con A-induced hepatitis and determine whether IL-37 overexpression could enhance the therapeutic effect of ERCs in this process.
ERCs were extracted from the menstrual blood of healthy female volunteer donors. The IL-37 gene was transferred into ERCs, and the expression of IL-37 in cells was detected by western blot and enzyme-linked immunosorbent assay. Hepatitis was induced by Con A in C57BL/6 mice that were randomly divided into groups treated with phosphate-buffered saline, ERCs, IL-37 or ERCs transfected with the IL-37 gene (IL-37-ERCs). Cell tracking, liver function, histopathological and immunohistological changes, immune cell proportions and levels of cytokines were measured 24 h after Con A administration.
Compared with ERC or IL-37 treatment, IL-37-ERCs further reduced levels of liver enzymes (alanine aminotransferase and aspartate aminotransferase) and improved histopathological changes in the liver. In addition, IL-37-ERC treatment further reduced the proportions of M1 macrophages and CD4+ T cells and increased the proportion of regulatory T cells. Moreover, IL-37-ERC treatment resulted in lower levels of IL-12 and interferon gamma, and higher level of transforming growth factor beta.
The results of this study suggest that ERCs can effectively alleviate Con A-induced hepatitis. Furthermore, IL-37 overexpression can significantly enhance the therapeutic efficacy of ERCs by augmenting the immunomodulatory and anti-inflammatory properties of ERCs. This study may provide a promising strategy for treatment of T-cell-dependent hepatitis.</description><subject>Animals</subject><subject>Biotechnology & Applied Microbiology</subject><subject>Cell & Tissue Engineering</subject><subject>Cell Biology</subject><subject>Concanavalin A</subject><subject>concanavalin A-induced hepatitis</subject><subject>Cytokines</subject><subject>endometrial regenerative cells</subject><subject>Endometrium</subject><subject>Female</subject><subject>Hematology</subject><subject>Hepatitis</subject><subject>IL-37</subject><subject>Life Sciences & Biomedicine</subject><subject>Liver</subject><subject>Medicine, Research & Experimental</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Research & Experimental Medicine</subject><subject>Science & Technology</subject><subject>T-cell-dependent liver injury</subject><issn>1465-3249</issn><issn>1477-2566</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><recordid>eNqNkUtr3DAURk1paNK0f6CLomWheCLLo4ehmzD0ERjoJlkLWb7qaPBIriRPmv76XjPTLEsXF73Od5GOqupdQ1cNbcTNfrW3T2XFKMMNtqJUvKiumrWUNeNCvFzmgtctW3eX1euc9xRBpfir6rJtedcKJa-q33fbupUkHiHBrylBzj4GAmFngoVMyg6WSmaCuXhLwDmwhUSHyBAPUJI3I0nwAwJCxR-BWBjHTHwgNgZrgjmaERe3tQ_DbGEgO5gQLD6_qS6cGTO8PY_X1cOXz_ebb_X2-9e7ze22ti0Xpe4c57xfcwG2bwYQVHDKBwltY3nXKwHKgTFOOgacKoaFZ7SXnRLMiN6219WHU98pxZ8z5KIPPi-3NAHinDXjTHEqRScRZSfUpphzAqen5A8mPemG6sW53uvFuV6c64ZpdI6h9-f-c3-A4TnyVzIC6gQ8Qh9dth7Q7TNGsYdoFVUNzqjc-IJ6YtjEORSMfvz_KNKfTjSgzqOHpM-JwSf8Nj1E_6-H_AGe1bWY</recordid><startdate>202107</startdate><enddate>202107</enddate><creator>Li, Guangming</creator><creator>Kong, Dejun</creator><creator>Qin, Yafei</creator><creator>Wang, Hongda</creator><creator>Hu, Yonghao</creator><creator>Zhao, Yiming</creator><creator>Hao, Jingpeng</creator><creator>Qin, Hong</creator><creator>Yu, Dingding</creator><creator>Zhu, Yanglin</creator><creator>Sun, Chenglu</creator><creator>Wang, Hao</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202107</creationdate><title>IL-37 overexpression enhances the therapeutic effect of endometrial regenerative cells in concanavalin A-induced hepatitis</title><author>Li, Guangming ; Kong, Dejun ; Qin, Yafei ; Wang, Hongda ; Hu, Yonghao ; Zhao, Yiming ; Hao, Jingpeng ; Qin, Hong ; Yu, Dingding ; Zhu, Yanglin ; Sun, Chenglu ; Wang, Hao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-9f555b456ecb1de606505d7e31c59b86e8feaaf7f2e50825087e30b79862a6bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Biotechnology & Applied Microbiology</topic><topic>Cell & Tissue Engineering</topic><topic>Cell Biology</topic><topic>Concanavalin A</topic><topic>concanavalin A-induced hepatitis</topic><topic>Cytokines</topic><topic>endometrial regenerative cells</topic><topic>Endometrium</topic><topic>Female</topic><topic>Hematology</topic><topic>Hepatitis</topic><topic>IL-37</topic><topic>Life Sciences & Biomedicine</topic><topic>Liver</topic><topic>Medicine, Research & Experimental</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Research & Experimental Medicine</topic><topic>Science & Technology</topic><topic>T-cell-dependent liver injury</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Guangming</creatorcontrib><creatorcontrib>Kong, Dejun</creatorcontrib><creatorcontrib>Qin, Yafei</creatorcontrib><creatorcontrib>Wang, Hongda</creatorcontrib><creatorcontrib>Hu, Yonghao</creatorcontrib><creatorcontrib>Zhao, Yiming</creatorcontrib><creatorcontrib>Hao, Jingpeng</creatorcontrib><creatorcontrib>Qin, Hong</creatorcontrib><creatorcontrib>Yu, Dingding</creatorcontrib><creatorcontrib>Zhu, Yanglin</creatorcontrib><creatorcontrib>Sun, Chenglu</creatorcontrib><creatorcontrib>Wang, Hao</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cytotherapy (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Guangming</au><au>Kong, Dejun</au><au>Qin, Yafei</au><au>Wang, Hongda</au><au>Hu, Yonghao</au><au>Zhao, Yiming</au><au>Hao, Jingpeng</au><au>Qin, Hong</au><au>Yu, Dingding</au><au>Zhu, Yanglin</au><au>Sun, Chenglu</au><au>Wang, Hao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-37 overexpression enhances the therapeutic effect of endometrial regenerative cells in concanavalin A-induced hepatitis</atitle><jtitle>Cytotherapy (Oxford, England)</jtitle><stitle>CYTOTHERAPY</stitle><addtitle>Cytotherapy</addtitle><date>2021-07</date><risdate>2021</risdate><volume>23</volume><issue>7</issue><spage>617</spage><epage>626</epage><pages>617-626</pages><issn>1465-3249</issn><eissn>1477-2566</eissn><abstract>Mesenchymal stromal cells and immunosuppressive factor IL-37 can both suppress concanavalin A (Con A)-induced hepatitis in mice. Endometrial regenerative cells (ERCs), novel types of mesenchymal-like stromal cells, possess powerful immunomodulatory effects and are effective in treating various diseases. The aim of this study was to explore the effects of ERCs in suppressing Con A-induced hepatitis and determine whether IL-37 overexpression could enhance the therapeutic effect of ERCs in this process.
ERCs were extracted from the menstrual blood of healthy female volunteer donors. The IL-37 gene was transferred into ERCs, and the expression of IL-37 in cells was detected by western blot and enzyme-linked immunosorbent assay. Hepatitis was induced by Con A in C57BL/6 mice that were randomly divided into groups treated with phosphate-buffered saline, ERCs, IL-37 or ERCs transfected with the IL-37 gene (IL-37-ERCs). Cell tracking, liver function, histopathological and immunohistological changes, immune cell proportions and levels of cytokines were measured 24 h after Con A administration.
Compared with ERC or IL-37 treatment, IL-37-ERCs further reduced levels of liver enzymes (alanine aminotransferase and aspartate aminotransferase) and improved histopathological changes in the liver. In addition, IL-37-ERC treatment further reduced the proportions of M1 macrophages and CD4+ T cells and increased the proportion of regulatory T cells. Moreover, IL-37-ERC treatment resulted in lower levels of IL-12 and interferon gamma, and higher level of transforming growth factor beta.
The results of this study suggest that ERCs can effectively alleviate Con A-induced hepatitis. Furthermore, IL-37 overexpression can significantly enhance the therapeutic efficacy of ERCs by augmenting the immunomodulatory and anti-inflammatory properties of ERCs. This study may provide a promising strategy for treatment of T-cell-dependent hepatitis.</abstract><cop>OXFORD</cop><pub>Elsevier Inc</pub><pmid>33593687</pmid><doi>10.1016/j.jcyt.2020.12.006</doi><tpages>10</tpages></addata></record> |
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| subjects | Animals Biotechnology & Applied Microbiology Cell & Tissue Engineering Cell Biology Concanavalin A concanavalin A-induced hepatitis Cytokines endometrial regenerative cells Endometrium Female Hematology Hepatitis IL-37 Life Sciences & Biomedicine Liver Medicine, Research & Experimental Mice Mice, Inbred C57BL Research & Experimental Medicine Science & Technology T-cell-dependent liver injury |
| title | IL-37 overexpression enhances the therapeutic effect of endometrial regenerative cells in concanavalin A-induced hepatitis |
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