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dc.contributor.authorShin, Eric Y.
dc.contributor.authorWang, Lanfang
dc.contributor.authorZemskova, Marina
dc.contributor.authorDeppen, Juline
dc.contributor.authorXu, Kai
dc.contributor.authorStrobel, Frederick
dc.contributor.authorGarcía, Andrés J.
dc.contributor.authorTirouvanziam, Rabindra
dc.contributor.authorLevit, Rebecca D.
dc.date.accessioned2018-05-16T18:20:19Z
dc.date.available2018-05-16T18:20:19Z
dc.date.issued2018-01-23
dc.identifier.citationShin, E. Y., Wang, L., Zemskova, M., Deppen, J., Xu, K., Strobel, F., . . . Levit, R. D. (2018). Adenosine Production by Biomaterial‐Supported Mesenchymal Stromal Cells Reduces the Innate Inflammatory Response in Myocardial Ischemia/Reperfusion Injury. Journal of the American Heart Association, 7(2). doi:10.1161/jaha.117.006949en_US
dc.identifier.issn2047-9980
dc.identifier.issn2047-9980
dc.identifier.pmid29331956
dc.identifier.doi10.1161/JAHA.117.006949
dc.identifier.urihttp://hdl.handle.net/10150/627656
dc.description.abstractBackgroundDuring myocardial ischemia/reperfusion (MI/R) injury, there is extensive release of immunogenic metabolites that activate cells of the innate immune system. These include ATP and AMP, which upregulate chemotaxis, migration, and effector function of early infiltrating inflammatory cells. These cells subsequently drive further tissue devitalization. Mesenchymal stromal cells (MSCs) are a potential treatment modality for MI/R because of their powerful anti-inflammatory capabilities; however, the manner in which they regulate the acute inflammatory milieu requires further elucidation. CD73, an ecto-5-nucleotidase, may be critical in regulating inflammation by converting pro-inflammatory AMP to anti-inflammatory adenosine. We hypothesized that MSC-mediated conversion of AMP into adenosine reduces inflammation in early MI/R, favoring a micro-environment that attenuates excessive innate immune cell activation and facilitates earlier cardiac recovery. Methods and ResultsAdult rats were subjected to 30minutes of MI/R injury. MSCs were encapsulated within a hydrogel vehicle and implanted onto the myocardium. A subset of MSCs were pretreated with the CD73 inhibitor, ,-methylene adenosine diphosphate, before implantation. Using liquid chromatography/mass spectrometry, we found that MSCs increase myocardial adenosine availability following injury via CD73 activity. MSCs also reduce innate immune cell infiltration as measured by flow cytometry, and hydrogen peroxide formation as measured by Amplex Red assay. These effects were dependent on MSC-mediated CD73 activity. Finally, through echocardiography we found that CD73 activity on MSCs was critical to optimal protection of cardiac function following MI/R injury. ConclusionsMSC-mediated conversion of AMP to adenosine by CD73 exerts a powerful anti-inflammatory effect critical for cardiac recovery following MI/R injury.en_US
dc.description.sponsorshipAmerican Heart Association Scientist Development Grant [14SDG18530001]; National Heart, Lung, and Blood Institute of the NIH [T32HL007745]en_US
dc.language.isoenen_US
dc.publisherWILEYen_US
dc.relation.urlhttp://jaha.ahajournals.org/lookup/doi/10.1161/JAHA.117.006949en_US
dc.rights© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License.en_US
dc.subjectcardioprotectionen_US
dc.subjectcell therapyen_US
dc.subjectinflammationen_US
dc.subjectischemiaen_US
dc.subjectischemia reperfusion injuryen_US
dc.subjectmesenchymal stem cellen_US
dc.subjectmyocardial inflammationen_US
dc.titleAdenosine Production by Biomaterial‐Supported Mesenchymal Stromal Cells Reduces the Innate Inflammatory Response in Myocardial Ischemia/Reperfusion Injuryen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Otolaryngol, Tucson, AZ USAen_US
dc.identifier.journalJOURNAL OF THE AMERICAN HEART ASSOCIATIONen_US
dc.description.noteOpen Access Journal; Creative Commons Attribution Non-Commercial Licenseen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleJournal of the American Heart Association
dc.source.volume7
dc.source.issue2
dc.source.beginpagee006949
refterms.dateFOA2018-05-16T18:20:20Z


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