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      Mesenchymal stromal cells mediate a switch to alternatively activated monocytes/macrophages after acute myocardial infarction.

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          Abstract

          Given the established anti-inflammatory properties of mesenchymal stromal cells (MSCs), we investigated their effect on inflammatory cell infiltration of ischemic cardiac tissue and cardiac function. We employed two types of MSCs, human bone marrow-derived (BM) MSCs and human umbilical cord perivascular cells in an experimental acute myocardial infarction (MI) model with the immune-deficient NOD/SCID gamma null mouse. Cells were infused 48 h after induction of MI and mice assessed 24 h later (72 h after MI) for bone marrow (BM), circulating and cardiac tissue-infiltrating monocytes/macrophages. We showed that in the presence of either MSC type, overall macrophage/monocyte levels were reduced, including pro-inflammatory M1-type macrophages, while the proportion of alternatively activated M2-type macrophages was significantly increased in the circulation and heart but not the BM. Moreover, we found decreased expression of IL-1β and IL-6, increased IL-10 expression and fewer apoptotic cardiomyocytes without changes in angiogenesis in the infarct area. Fractional shortening was enhanced 2 weeks after cell infusion but was similar to medium controls 16 weeks after MI. In vitro studies showed that BM MSCs increased the frequency of alternatively activated monocytes/macrophages, in part by MSC-mediated secretion of IL-10. Our data suggest a new mechanism for MSC-mediated enhancement of cardiac function, possibly via an IL-10 mediated switch from infiltration of pro-inflammatory to anti-inflammatory macrophages at the infarct site. Additional studies are warranted confirming the role of IL-10 and augmenting the anti-inflammatory effects of MSCs in cardiac regeneration.

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          Author and article information

          Journal
          Basic Res Cardiol
          Basic research in cardiology
          Springer Science and Business Media LLC
          1435-1803
          0300-8428
          Nov 2011
          : 106
          : 6
          Affiliations
          [1 ] Cell Therapy Program, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada. victor_dayan@hotmail.com
          Article
          10.1007/s00395-011-0221-9
          21901289
          a9780567-193f-4da9-814d-885328b84905
          History

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