The conditioned medium of human mesenchymal stromal cells reduces irradiation-induced damage in cardiac fibroblast cells
Recently, multipotent mesenchymal stromal cell (MSC) treatment has attracted special attention as a new alternative strategy for stimulating regeneration. Irradiation myocardial fibrosis (IMF) is a major complication associated with total body irradiation for hematopoietic stem cell transplantation,...
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Veröffentlicht in: | Journal of radiation research 2018-09, Vol.59 (5), p.555-564 |
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description | Recently, multipotent mesenchymal stromal cell (MSC) treatment has attracted special attention as a new alternative strategy for stimulating regeneration. Irradiation myocardial fibrosis (IMF) is a major complication associated with total body irradiation for hematopoietic stem cell transplantation, nuclear accidents, and thoracic radiotherapy for lung cancer, esophageal cancer, proximal gastric cancer, breast cancer, thymoma, and lymphoma. The aim of the present study was to assess the therapeutic paracrine effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in the cell model of IMF. For this purpose, primary human cardiac fibroblasts (HCF) cells were irradiated and cultured with the conditioned medium of UC-MSCs (MSCCM). MSCCM promoted cell viability, reduced collagen deposition as measured by Sircol assay and qPCR (Col1A1 and Col1A2), prevented oxidative stress and increased antioxidant status (as measured by malondialdehyde content and the activities and mRNA levels of antioxidant enzymes), and reduced pro-fibrotic TGF-β1, IL-6 and IL-8 levels (as examined by ELISA kit and qPCR). Pretreatment with inhibitor of NF-κB led to a decrease in the levels of TGF-β1 in cell lysate of HCF cells by ELISA kit. Furthermore, we also found that MSCCM prevented NF-κB signaling pathway activation for its proinflammatory actions induced by irradiation. Taken together, our data suggest that MSCCM could reduce irradiation-induced TGF-β1 production through inhibition of the NF-κB signaling pathway. These data provide new insights into the functional actions of MSCCM on irradiation myocardial fibrosis. |
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Irradiation myocardial fibrosis (IMF) is a major complication associated with total body irradiation for hematopoietic stem cell transplantation, nuclear accidents, and thoracic radiotherapy for lung cancer, esophageal cancer, proximal gastric cancer, breast cancer, thymoma, and lymphoma. The aim of the present study was to assess the therapeutic paracrine effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in the cell model of IMF. For this purpose, primary human cardiac fibroblasts (HCF) cells were irradiated and cultured with the conditioned medium of UC-MSCs (MSCCM). MSCCM promoted cell viability, reduced collagen deposition as measured by Sircol assay and qPCR (Col1A1 and Col1A2), prevented oxidative stress and increased antioxidant status (as measured by malondialdehyde content and the activities and mRNA levels of antioxidant enzymes), and reduced pro-fibrotic TGF-β1, IL-6 and IL-8 levels (as examined by ELISA kit and qPCR). Pretreatment with inhibitor of NF-κB led to a decrease in the levels of TGF-β1 in cell lysate of HCF cells by ELISA kit. Furthermore, we also found that MSCCM prevented NF-κB signaling pathway activation for its proinflammatory actions induced by irradiation. Taken together, our data suggest that MSCCM could reduce irradiation-induced TGF-β1 production through inhibition of the NF-κB signaling pathway. These data provide new insights into the functional actions of MSCCM on irradiation myocardial fibrosis.</description><identifier>ISSN: 0449-3060</identifier><identifier>EISSN: 1349-9157</identifier><identifier>DOI: 10.1093/jrr/rry048</identifier><identifier>PMID: 30010837</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Antioxidants - metabolism ; Cell Proliferation - drug effects ; Cell Survival ; Collagen Type I - metabolism ; Collagen Type XI - metabolism ; Culture Media, Conditioned - chemistry ; Fibroblasts - cytology ; Fibroblasts - radiation effects ; Humans ; Inflammation ; Lipid Peroxidation ; Mesenchymal Stem Cells - cytology ; Myocardium - cytology ; NF-kappa B - metabolism ; Oxidative Stress ; Radiation Injuries ; Regular Paper ; RNA, Messenger - metabolism ; Signal Transduction ; Transforming Growth Factor beta1 - metabolism ; Umbilical Cord - cytology</subject><ispartof>Journal of radiation research, 2018-09, Vol.59 (5), p.555-564</ispartof><rights>The Author(s) 2018. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-a26845884a251a3dcbfefd8e5b705ccac6c45d87bcdda888e826044eed1fc5b73</citedby><cites>FETCH-LOGICAL-c402t-a26845884a251a3dcbfefd8e5b705ccac6c45d87bcdda888e826044eed1fc5b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151644/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151644/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30010837$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Zhu-Yue</creatorcontrib><creatorcontrib>Hu, Ying-Ying</creatorcontrib><creatorcontrib>Hu, Xiao-Fan</creatorcontrib><creatorcontrib>Cheng, Long-Xian</creatorcontrib><title>The conditioned medium of human mesenchymal stromal cells reduces irradiation-induced damage in cardiac fibroblast cells</title><title>Journal of radiation research</title><addtitle>J Radiat Res</addtitle><description>Recently, multipotent mesenchymal stromal cell (MSC) treatment has attracted special attention as a new alternative strategy for stimulating regeneration. Irradiation myocardial fibrosis (IMF) is a major complication associated with total body irradiation for hematopoietic stem cell transplantation, nuclear accidents, and thoracic radiotherapy for lung cancer, esophageal cancer, proximal gastric cancer, breast cancer, thymoma, and lymphoma. The aim of the present study was to assess the therapeutic paracrine effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in the cell model of IMF. For this purpose, primary human cardiac fibroblasts (HCF) cells were irradiated and cultured with the conditioned medium of UC-MSCs (MSCCM). MSCCM promoted cell viability, reduced collagen deposition as measured by Sircol assay and qPCR (Col1A1 and Col1A2), prevented oxidative stress and increased antioxidant status (as measured by malondialdehyde content and the activities and mRNA levels of antioxidant enzymes), and reduced pro-fibrotic TGF-β1, IL-6 and IL-8 levels (as examined by ELISA kit and qPCR). Pretreatment with inhibitor of NF-κB led to a decrease in the levels of TGF-β1 in cell lysate of HCF cells by ELISA kit. Furthermore, we also found that MSCCM prevented NF-κB signaling pathway activation for its proinflammatory actions induced by irradiation. Taken together, our data suggest that MSCCM could reduce irradiation-induced TGF-β1 production through inhibition of the NF-κB signaling pathway. These data provide new insights into the functional actions of MSCCM on irradiation myocardial fibrosis.</description><subject>Antioxidants - metabolism</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival</subject><subject>Collagen Type I - metabolism</subject><subject>Collagen Type XI - metabolism</subject><subject>Culture Media, Conditioned - chemistry</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - radiation effects</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Lipid Peroxidation</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Myocardium - cytology</subject><subject>NF-kappa B - metabolism</subject><subject>Oxidative Stress</subject><subject>Radiation Injuries</subject><subject>Regular Paper</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><subject>Umbilical Cord - cytology</subject><issn>0449-3060</issn><issn>1349-9157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1O3TAQha2qVbnQbvoAlZcVUmCcOImzQUKo_EhIbOjamtgTrlFig52g3rfH0QXUrsb2fHPGR4exHwJOBHTV6WOMpzHuQKpPbCMq2RWdqNvPbAMynyto4IAdpvQIULZQw1d2UAEIUFW7YX_vt8RN8NbNLniyfCLrlomHgW-XCX2-J_Jmu5tw5GmOYa2GxjHxSHYxlLiLEa3Ddb5wfn2z3OKED8Sd5wZjbho-uD6GfsQ078e_sS8Djom-v9Uj9ufy9_3FdXF7d3VzcX5bGAnlXGDZKFkrJbGsBVbW9AMNVlHdZyvGoGmMrK1qe2MtKqVIlU22TWTFYDJUHbGzve7T0mdvhvwccdRP0U0Ydzqg0_93vNvqh_CiG1GLRsos8OtNIIbnhdKsJ5dWC-gpLEmX0ELbdaoVGT3eoyaGlCINH2sE6DUqnaPS-6gy_PPfj32g79lUr8_IlWI</recordid><startdate>20180901</startdate><enddate>20180901</enddate><creator>Chen, Zhu-Yue</creator><creator>Hu, Ying-Ying</creator><creator>Hu, Xiao-Fan</creator><creator>Cheng, Long-Xian</creator><general>Oxford University Press</general><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><scope>5PM</scope></search><sort><creationdate>20180901</creationdate><title>The conditioned medium of human mesenchymal stromal cells reduces irradiation-induced damage in cardiac fibroblast cells</title><author>Chen, Zhu-Yue ; Hu, Ying-Ying ; Hu, Xiao-Fan ; Cheng, Long-Xian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-a26845884a251a3dcbfefd8e5b705ccac6c45d87bcdda888e826044eed1fc5b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Antioxidants - metabolism</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival</topic><topic>Collagen Type I - metabolism</topic><topic>Collagen Type XI - metabolism</topic><topic>Culture Media, Conditioned - chemistry</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - radiation effects</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Lipid Peroxidation</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Myocardium - cytology</topic><topic>NF-kappa B - metabolism</topic><topic>Oxidative Stress</topic><topic>Radiation Injuries</topic><topic>Regular Paper</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction</topic><topic>Transforming Growth Factor beta1 - metabolism</topic><topic>Umbilical Cord - cytology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Zhu-Yue</creatorcontrib><creatorcontrib>Hu, Ying-Ying</creatorcontrib><creatorcontrib>Hu, Xiao-Fan</creatorcontrib><creatorcontrib>Cheng, Long-Xian</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of radiation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Zhu-Yue</au><au>Hu, Ying-Ying</au><au>Hu, Xiao-Fan</au><au>Cheng, Long-Xian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The conditioned medium of human mesenchymal stromal cells reduces irradiation-induced damage in cardiac fibroblast cells</atitle><jtitle>Journal of radiation research</jtitle><addtitle>J Radiat Res</addtitle><date>2018-09-01</date><risdate>2018</risdate><volume>59</volume><issue>5</issue><spage>555</spage><epage>564</epage><pages>555-564</pages><issn>0449-3060</issn><eissn>1349-9157</eissn><abstract>Recently, multipotent mesenchymal stromal cell (MSC) treatment has attracted special attention as a new alternative strategy for stimulating regeneration. Irradiation myocardial fibrosis (IMF) is a major complication associated with total body irradiation for hematopoietic stem cell transplantation, nuclear accidents, and thoracic radiotherapy for lung cancer, esophageal cancer, proximal gastric cancer, breast cancer, thymoma, and lymphoma. The aim of the present study was to assess the therapeutic paracrine effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in the cell model of IMF. For this purpose, primary human cardiac fibroblasts (HCF) cells were irradiated and cultured with the conditioned medium of UC-MSCs (MSCCM). MSCCM promoted cell viability, reduced collagen deposition as measured by Sircol assay and qPCR (Col1A1 and Col1A2), prevented oxidative stress and increased antioxidant status (as measured by malondialdehyde content and the activities and mRNA levels of antioxidant enzymes), and reduced pro-fibrotic TGF-β1, IL-6 and IL-8 levels (as examined by ELISA kit and qPCR). Pretreatment with inhibitor of NF-κB led to a decrease in the levels of TGF-β1 in cell lysate of HCF cells by ELISA kit. Furthermore, we also found that MSCCM prevented NF-κB signaling pathway activation for its proinflammatory actions induced by irradiation. Taken together, our data suggest that MSCCM could reduce irradiation-induced TGF-β1 production through inhibition of the NF-κB signaling pathway. These data provide new insights into the functional actions of MSCCM on irradiation myocardial fibrosis.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>30010837</pmid><doi>10.1093/jrr/rry048</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Antioxidants - metabolism Cell Proliferation - drug effects Cell Survival Collagen Type I - metabolism Collagen Type XI - metabolism Culture Media, Conditioned - chemistry Fibroblasts - cytology Fibroblasts - radiation effects Humans Inflammation Lipid Peroxidation Mesenchymal Stem Cells - cytology Myocardium - cytology NF-kappa B - metabolism Oxidative Stress Radiation Injuries Regular Paper RNA, Messenger - metabolism Signal Transduction Transforming Growth Factor beta1 - metabolism Umbilical Cord - cytology |
title | The conditioned medium of human mesenchymal stromal cells reduces irradiation-induced damage in cardiac fibroblast cells |
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