Mesenchymal Stem Cells Secrete Immunologically Active Exosomes
Mesenchymal stem cells (MSCs) have been shown to secrete exosomes that are cardioprotective. Here, we demonstrated that MSC exosome, a secreted membrane vesicle, is immunologically active. MSC exosomes induced polymyxin-resistant, MYD88-dependent secreted embryonic alkaline phosphatase (SEAP) expres...
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| Veröffentlicht in: | Stem cells and development 2014-06, Vol.23 (11), p.1233-1244 |
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| creator | Zhang, Bin Yin, Yijun Lai, Ruenn Chai Tan, Soon Sim Choo, Andre Boon Hwa Lim, Sai Kiang |
| description | Mesenchymal stem cells (MSCs) have been shown to secrete exosomes that are cardioprotective. Here, we demonstrated that MSC exosome, a secreted membrane vesicle, is immunologically active. MSC exosomes induced polymyxin-resistant, MYD88-dependent secreted embryonic alkaline phosphatase (SEAP) expression in a THP1-Xblue, a THP-1 reporter cell line with an NFκB-SEAP reporter gene. In contrast to lipopolysaccharide, they induced high levels of anti-inflammatory
IL10
and
TGFβ1
transcript at 3 and 72 h, and much attenuated levels of pro-inflammatory
IL1B, IL6, TNFA
and
IL12P40
transcript at 3-h. The 3-h but not 72-h induction of cytokine transcript was abrogated by MyD88 deficiency. Primary human and mouse monocytes exhibited a similar exosome-induced cytokine transcript profile. Exosome-treated THP-1 but not MyD88-deficient THP-1 cells polarized activated CD4
+
T cells to CD4
+
CD25
+
FoxP3
+
regulatory T cells (Tregs) at a ratio of one exosome-treated THP-1 cell to 1,000 CD4
+
T cells. Infusion of MSC exosomes enhanced the survival of allogenic skin graft in mice and increased Tregs. |
| doi_str_mv | 10.1089/scd.2013.0479 |
| format | Article |
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IL10
and
TGFβ1
transcript at 3 and 72 h, and much attenuated levels of pro-inflammatory
IL1B, IL6, TNFA
and
IL12P40
transcript at 3-h. The 3-h but not 72-h induction of cytokine transcript was abrogated by MyD88 deficiency. Primary human and mouse monocytes exhibited a similar exosome-induced cytokine transcript profile. Exosome-treated THP-1 but not MyD88-deficient THP-1 cells polarized activated CD4
+
T cells to CD4
+
CD25
+
FoxP3
+
regulatory T cells (Tregs) at a ratio of one exosome-treated THP-1 cell to 1,000 CD4
+
T cells. Infusion of MSC exosomes enhanced the survival of allogenic skin graft in mice and increased Tregs.</description><identifier>ISSN: 1547-3287</identifier><identifier>EISSN: 1557-8534</identifier><identifier>DOI: 10.1089/scd.2013.0479</identifier><identifier>PMID: 24367916</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Animals ; Cell Differentiation - immunology ; Cells, Cultured ; Exosomes - immunology ; Exosomes - metabolism ; HEK293 Cells ; Humans ; Immunity - physiology ; Mesenchymal Stromal Cells - immunology ; Mesenchymal Stromal Cells - secretion ; Mice ; Mice, Inbred BALB C ; Myeloid Differentiation Factor 88 - physiology ; Original Research Reports ; Signal Transduction ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - metabolism ; Toll-Like Receptors - physiology</subject><ispartof>Stem cells and development, 2014-06, Vol.23 (11), p.1233-1244</ispartof><rights>2014, Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c337t-2e6b3858c861ec09876901ba9a6bf82366562c4d5b0ed1a42437492673b066ad3</citedby><cites>FETCH-LOGICAL-c337t-2e6b3858c861ec09876901ba9a6bf82366562c4d5b0ed1a42437492673b066ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24367916$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Yin, Yijun</creatorcontrib><creatorcontrib>Lai, Ruenn Chai</creatorcontrib><creatorcontrib>Tan, Soon Sim</creatorcontrib><creatorcontrib>Choo, Andre Boon Hwa</creatorcontrib><creatorcontrib>Lim, Sai Kiang</creatorcontrib><title>Mesenchymal Stem Cells Secrete Immunologically Active Exosomes</title><title>Stem cells and development</title><addtitle>Stem Cells Dev</addtitle><description>Mesenchymal stem cells (MSCs) have been shown to secrete exosomes that are cardioprotective. Here, we demonstrated that MSC exosome, a secreted membrane vesicle, is immunologically active. MSC exosomes induced polymyxin-resistant, MYD88-dependent secreted embryonic alkaline phosphatase (SEAP) expression in a THP1-Xblue, a THP-1 reporter cell line with an NFκB-SEAP reporter gene. In contrast to lipopolysaccharide, they induced high levels of anti-inflammatory
IL10
and
TGFβ1
transcript at 3 and 72 h, and much attenuated levels of pro-inflammatory
IL1B, IL6, TNFA
and
IL12P40
transcript at 3-h. The 3-h but not 72-h induction of cytokine transcript was abrogated by MyD88 deficiency. Primary human and mouse monocytes exhibited a similar exosome-induced cytokine transcript profile. Exosome-treated THP-1 but not MyD88-deficient THP-1 cells polarized activated CD4
+
T cells to CD4
+
CD25
+
FoxP3
+
regulatory T cells (Tregs) at a ratio of one exosome-treated THP-1 cell to 1,000 CD4
+
T cells. Infusion of MSC exosomes enhanced the survival of allogenic skin graft in mice and increased Tregs.</description><subject>Animals</subject><subject>Cell Differentiation - immunology</subject><subject>Cells, Cultured</subject><subject>Exosomes - immunology</subject><subject>Exosomes - metabolism</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Immunity - physiology</subject><subject>Mesenchymal Stromal Cells - immunology</subject><subject>Mesenchymal Stromal Cells - secretion</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Myeloid Differentiation Factor 88 - physiology</subject><subject>Original Research Reports</subject><subject>Signal Transduction</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>Toll-Like Receptors - physiology</subject><issn>1547-3287</issn><issn>1557-8534</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkD1PwzAQhi0EoqUwsqKMLCn-trMgVVWBSkUMhdlynCsE2UmJE9T-exK1sDLd6fTo1XsPQtcETwnW2V10xZRiwqaYq-wEjYkQKtWC8dNh5yplVKsRuojxE2MqqebnaEQ5kyojcozunyFC5T72wfpk3UJI5uB9TNbgGmghWYbQVbWv30tnvd8nM9eW35AsdnWsA8RLdLaxPsLVcU7Q28Pidf6Url4el_PZKnWMqTalIHOmhXZaEnA400pmmOQ2szLfaMqkFJI6XogcQ0Es7_spnlGpWI6ltAWboNtD7rapvzqIrQlldH1TW0HdRUME1YyJ_sEeTQ-oa-oYG9iYbVMG2-wNwWZQZnplZlBmBmU9f3OM7vIAxR_966gH2AEYzraqfAk5NO0_sT8uOXb2</recordid><startdate>20140601</startdate><enddate>20140601</enddate><creator>Zhang, Bin</creator><creator>Yin, Yijun</creator><creator>Lai, Ruenn Chai</creator><creator>Tan, Soon Sim</creator><creator>Choo, Andre Boon Hwa</creator><creator>Lim, Sai Kiang</creator><general>Mary Ann Liebert, Inc</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></search><sort><creationdate>20140601</creationdate><title>Mesenchymal Stem Cells Secrete Immunologically Active Exosomes</title><author>Zhang, Bin ; Yin, Yijun ; Lai, Ruenn Chai ; Tan, Soon Sim ; Choo, Andre Boon Hwa ; Lim, Sai Kiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c337t-2e6b3858c861ec09876901ba9a6bf82366562c4d5b0ed1a42437492673b066ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Cell Differentiation - immunology</topic><topic>Cells, Cultured</topic><topic>Exosomes - immunology</topic><topic>Exosomes - metabolism</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Immunity - physiology</topic><topic>Mesenchymal Stromal Cells - immunology</topic><topic>Mesenchymal Stromal Cells - secretion</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Myeloid Differentiation Factor 88 - physiology</topic><topic>Original Research Reports</topic><topic>Signal Transduction</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>Toll-Like Receptors - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Yin, Yijun</creatorcontrib><creatorcontrib>Lai, Ruenn Chai</creatorcontrib><creatorcontrib>Tan, Soon Sim</creatorcontrib><creatorcontrib>Choo, Andre Boon Hwa</creatorcontrib><creatorcontrib>Lim, Sai Kiang</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><jtitle>Stem cells and development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Bin</au><au>Yin, Yijun</au><au>Lai, Ruenn Chai</au><au>Tan, Soon Sim</au><au>Choo, Andre Boon Hwa</au><au>Lim, Sai Kiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mesenchymal Stem Cells Secrete Immunologically Active Exosomes</atitle><jtitle>Stem cells and development</jtitle><addtitle>Stem Cells Dev</addtitle><date>2014-06-01</date><risdate>2014</risdate><volume>23</volume><issue>11</issue><spage>1233</spage><epage>1244</epage><pages>1233-1244</pages><issn>1547-3287</issn><eissn>1557-8534</eissn><abstract>Mesenchymal stem cells (MSCs) have been shown to secrete exosomes that are cardioprotective. Here, we demonstrated that MSC exosome, a secreted membrane vesicle, is immunologically active. MSC exosomes induced polymyxin-resistant, MYD88-dependent secreted embryonic alkaline phosphatase (SEAP) expression in a THP1-Xblue, a THP-1 reporter cell line with an NFκB-SEAP reporter gene. In contrast to lipopolysaccharide, they induced high levels of anti-inflammatory
IL10
and
TGFβ1
transcript at 3 and 72 h, and much attenuated levels of pro-inflammatory
IL1B, IL6, TNFA
and
IL12P40
transcript at 3-h. The 3-h but not 72-h induction of cytokine transcript was abrogated by MyD88 deficiency. Primary human and mouse monocytes exhibited a similar exosome-induced cytokine transcript profile. Exosome-treated THP-1 but not MyD88-deficient THP-1 cells polarized activated CD4
+
T cells to CD4
+
CD25
+
FoxP3
+
regulatory T cells (Tregs) at a ratio of one exosome-treated THP-1 cell to 1,000 CD4
+
T cells. Infusion of MSC exosomes enhanced the survival of allogenic skin graft in mice and increased Tregs.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>24367916</pmid><doi>10.1089/scd.2013.0479</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1547-3287 |
| ispartof | Stem cells and development, 2014-06, Vol.23 (11), p.1233-1244 |
| issn | 1547-3287 1557-8534 |
| language | eng |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Animals Cell Differentiation - immunology Cells, Cultured Exosomes - immunology Exosomes - metabolism HEK293 Cells Humans Immunity - physiology Mesenchymal Stromal Cells - immunology Mesenchymal Stromal Cells - secretion Mice Mice, Inbred BALB C Myeloid Differentiation Factor 88 - physiology Original Research Reports Signal Transduction T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism Toll-Like Receptors - physiology |
| title | Mesenchymal Stem Cells Secrete Immunologically Active Exosomes |
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