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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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Acknowledgments

This research is supported by the Orsino Translational Research Laboratory at Princess Margaret Hospital. AK holds the Gloria and Seymour Epstein Chair in Cell Therapy and Transplantation at University Health Network and the University of Toronto.

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Authors and Affiliations

  1. Cell Therapy Program, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada

    Victor Dayan, Gustavo Yannarelli, Paola Filomeno, Xing-Hua Wang & Armand Keating

  2. Division of Cardiology, Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Canada

    Filio Billia

  3. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada

    John E. Davies & Armand Keating

  4. 26 de Marzo 3459/602, Montevideo, Uruguay

    Victor Dayan

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  1. Victor Dayan
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Correspondence to Victor Dayan.

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Dayan, V., Yannarelli, G., Billia, F. et al. Mesenchymal stromal cells mediate a switch to alternatively activated monocytes/macrophages after acute myocardial infarction. Basic Res Cardiol 106, 1299–1310 (2011). https://doi.org/10.1007/s00395-011-0221-9

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  • DOI: https://doi.org/10.1007/s00395-011-0221-9

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