Species Variation in the Mechanisms of Mesenchymal Stem Cell‐Mediated Immunosuppression
Bone marrow‐derived mesenchymal stem cells (MSCs) hold great promise for treating immune disorders because of their immunoregulatory capacity, but the mechanism remains controversial. As we show here, the mechanism of MSC‐mediated immunosuppression varies among different species. Immunosuppression b...
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| Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 2009-08, Vol.27 (8), p.1954-1962 |
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| container_title | Stem cells (Dayton, Ohio) |
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| creator | Ren, Guangwen Su, Juanjuan Zhang, Liying Zhao, Xin Ling, Weifang L'huillie, Andrew Zhang, Jimin Lu, Yongqing Roberts, Arthur I. Ji, Weizhi Zhang, Huatang Rabson, Arnold B. Shi, Yufang |
| description | Bone marrow‐derived mesenchymal stem cells (MSCs) hold great promise for treating immune disorders because of their immunoregulatory capacity, but the mechanism remains controversial. As we show here, the mechanism of MSC‐mediated immunosuppression varies among different species. Immunosuppression by human‐ or monkey‐derived MSCs is mediated by indoleamine 2,3‐dioxygenase (IDO), whereas mouse MSCs utilize nitric oxide, under the same culture conditions. When the expression of IDO and inducible nitric oxide synthase (iNOS) were examined in human and mouse MSCs after stimulation with their respective inflammatory cytokines, we found that human MSCs expressed extremely high levels of IDO, and very low levels of iNOS, whereas mouse MSCs expressed abundant iNOS and very little IDO. Immunosuppression by human MSCs was not intrinsic, but was induced by inflammatory cytokines and was chemokine‐dependent, as it is in mouse. These findings provide critical information about the immunosuppression of MSCs and for better application of MSCs in treating immune disorders. STEM CELLS 2009;27:1954–1962 |
| doi_str_mv | 10.1002/stem.118 |
| format | Article |
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As we show here, the mechanism of MSC‐mediated immunosuppression varies among different species. Immunosuppression by human‐ or monkey‐derived MSCs is mediated by indoleamine 2,3‐dioxygenase (IDO), whereas mouse MSCs utilize nitric oxide, under the same culture conditions. When the expression of IDO and inducible nitric oxide synthase (iNOS) were examined in human and mouse MSCs after stimulation with their respective inflammatory cytokines, we found that human MSCs expressed extremely high levels of IDO, and very low levels of iNOS, whereas mouse MSCs expressed abundant iNOS and very little IDO. Immunosuppression by human MSCs was not intrinsic, but was induced by inflammatory cytokines and was chemokine‐dependent, as it is in mouse. These findings provide critical information about the immunosuppression of MSCs and for better application of MSCs in treating immune disorders. 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As we show here, the mechanism of MSC‐mediated immunosuppression varies among different species. Immunosuppression by human‐ or monkey‐derived MSCs is mediated by indoleamine 2,3‐dioxygenase (IDO), whereas mouse MSCs utilize nitric oxide, under the same culture conditions. When the expression of IDO and inducible nitric oxide synthase (iNOS) were examined in human and mouse MSCs after stimulation with their respective inflammatory cytokines, we found that human MSCs expressed extremely high levels of IDO, and very low levels of iNOS, whereas mouse MSCs expressed abundant iNOS and very little IDO. Immunosuppression by human MSCs was not intrinsic, but was induced by inflammatory cytokines and was chemokine‐dependent, as it is in mouse. These findings provide critical information about the immunosuppression of MSCs and for better application of MSCs in treating immune disorders. STEM CELLS 2009;27:1954–1962</description><subject>Animals</subject><subject>Chemokine</subject><subject>Cytokines - immunology</subject><subject>Cytokines - metabolism</subject><subject>Humans</subject><subject>Immune Tolerance</subject><subject>Immunosuppression</subject><subject>Indoleamine 2,3‐dioxygenase</subject><subject>Indoleamine-Pyrrole 2,3,-Dioxygenase - immunology</subject><subject>Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism</subject><subject>Macaca mulatta</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Mesenchymal Stem Cells - immunology</subject><subject>Mesenchymal Stem Cells - physiology</subject><subject>Mice</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - immunology</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide Synthase Type II - immunology</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Species Specificity</subject><issn>1066-5099</issn><issn>1549-4918</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEFLwzAUx4MoTqfgJ5Dc9NKZNEmTHGVMHWx42BQ8lS55ZZWmrU2L7OZH8DP6SUzZwJOnvPB-7_cef4SuKJlQQuI734GbUKqO0BkVXEdcU3UcapIkkSBaj9C59--EUC6UOkUjqgXnPJZn6G3VgCnA49esLbKuqCtcVLjbAl6C2WZV4Z3HdR5-Hiqz3bmsxKuwDU-hLH--vpdgwxhYPHeur2rfN00L3gfPBTrJs9LD5eEdo5eH2Xr6FC2eH-fT-0VkeExURI0QGx5rJrmVTOVApAwNFhuda84TFXObU6KkyGVsFdHWWMWIik1CGVWSjdHN3tu09UcPvktd4U24Lqug7n0qGSdMUDGQt3vStLX3LeRp0xYua3cpJemQYzrkmIYcA3p9kPYbB_YPPAQXgGgPfBYl7P4Vpav1bDkIfwHu_ny-</recordid><startdate>200908</startdate><enddate>200908</enddate><creator>Ren, Guangwen</creator><creator>Su, Juanjuan</creator><creator>Zhang, Liying</creator><creator>Zhao, Xin</creator><creator>Ling, Weifang</creator><creator>L'huillie, Andrew</creator><creator>Zhang, Jimin</creator><creator>Lu, Yongqing</creator><creator>Roberts, Arthur I.</creator><creator>Ji, Weizhi</creator><creator>Zhang, Huatang</creator><creator>Rabson, Arnold B.</creator><creator>Shi, Yufang</creator><general>Wiley Subscription Services, Inc., A Wiley Company</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>200908</creationdate><title>Species Variation in the Mechanisms of Mesenchymal Stem Cell‐Mediated Immunosuppression</title><author>Ren, Guangwen ; Su, Juanjuan ; Zhang, Liying ; Zhao, Xin ; Ling, Weifang ; L'huillie, Andrew ; Zhang, Jimin ; Lu, Yongqing ; Roberts, Arthur I. ; Ji, Weizhi ; Zhang, Huatang ; Rabson, Arnold B. ; Shi, Yufang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4208-1c55b429374d738fe07742032c9f9446824df10875f72d809dcd83082c6131873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Chemokine</topic><topic>Cytokines - immunology</topic><topic>Cytokines - metabolism</topic><topic>Humans</topic><topic>Immune Tolerance</topic><topic>Immunosuppression</topic><topic>Indoleamine 2,3‐dioxygenase</topic><topic>Indoleamine-Pyrrole 2,3,-Dioxygenase - immunology</topic><topic>Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism</topic><topic>Macaca mulatta</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mesenchymal Stem Cells - immunology</topic><topic>Mesenchymal Stem Cells - physiology</topic><topic>Mice</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - immunology</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Synthase Type II - immunology</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Species Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ren, Guangwen</creatorcontrib><creatorcontrib>Su, Juanjuan</creatorcontrib><creatorcontrib>Zhang, Liying</creatorcontrib><creatorcontrib>Zhao, Xin</creatorcontrib><creatorcontrib>Ling, Weifang</creatorcontrib><creatorcontrib>L'huillie, Andrew</creatorcontrib><creatorcontrib>Zhang, Jimin</creatorcontrib><creatorcontrib>Lu, Yongqing</creatorcontrib><creatorcontrib>Roberts, Arthur I.</creatorcontrib><creatorcontrib>Ji, Weizhi</creatorcontrib><creatorcontrib>Zhang, Huatang</creatorcontrib><creatorcontrib>Rabson, Arnold B.</creatorcontrib><creatorcontrib>Shi, Yufang</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 (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ren, Guangwen</au><au>Su, Juanjuan</au><au>Zhang, Liying</au><au>Zhao, Xin</au><au>Ling, Weifang</au><au>L'huillie, Andrew</au><au>Zhang, Jimin</au><au>Lu, Yongqing</au><au>Roberts, Arthur I.</au><au>Ji, Weizhi</au><au>Zhang, Huatang</au><au>Rabson, Arnold B.</au><au>Shi, Yufang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Species Variation in the Mechanisms of Mesenchymal Stem Cell‐Mediated Immunosuppression</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>2009-08</date><risdate>2009</risdate><volume>27</volume><issue>8</issue><spage>1954</spage><epage>1962</epage><pages>1954-1962</pages><issn>1066-5099</issn><issn>1549-4918</issn><eissn>1549-4918</eissn><abstract>Bone marrow‐derived mesenchymal stem cells (MSCs) hold great promise for treating immune disorders because of their immunoregulatory capacity, but the mechanism remains controversial. As we show here, the mechanism of MSC‐mediated immunosuppression varies among different species. Immunosuppression by human‐ or monkey‐derived MSCs is mediated by indoleamine 2,3‐dioxygenase (IDO), whereas mouse MSCs utilize nitric oxide, under the same culture conditions. When the expression of IDO and inducible nitric oxide synthase (iNOS) were examined in human and mouse MSCs after stimulation with their respective inflammatory cytokines, we found that human MSCs expressed extremely high levels of IDO, and very low levels of iNOS, whereas mouse MSCs expressed abundant iNOS and very little IDO. Immunosuppression by human MSCs was not intrinsic, but was induced by inflammatory cytokines and was chemokine‐dependent, as it is in mouse. These findings provide critical information about the immunosuppression of MSCs and for better application of MSCs in treating immune disorders. STEM CELLS 2009;27:1954–1962</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19544427</pmid><doi>10.1002/stem.118</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Chemokine Cytokines - immunology Cytokines - metabolism Humans Immune Tolerance Immunosuppression Indoleamine 2,3‐dioxygenase Indoleamine-Pyrrole 2,3,-Dioxygenase - immunology Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism Macaca mulatta Mesenchymal Stem Cell Transplantation Mesenchymal stem cells Mesenchymal Stem Cells - cytology Mesenchymal Stem Cells - immunology Mesenchymal Stem Cells - physiology Mice Nitric oxide Nitric Oxide - immunology Nitric Oxide - metabolism Nitric Oxide Synthase Type II - immunology Nitric Oxide Synthase Type II - metabolism Species Specificity |
| title | Species Variation in the Mechanisms of Mesenchymal Stem Cell‐Mediated Immunosuppression |
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