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

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.

Brief Report: The Potential Role of Epigenetics on Multipotent Cell Differentiation Capacity of Mesenchymal Stromal Cells

“…Human MSCs derived from embryonic and fetal sources have also exhibited the ability to enhance cardiomyogenesis compared with their adult counterparts [17]. Moreover, several reports have recently demonstrated the regenerative potential of HUCPVCs in different animal models [18][19][20]. Taken together, these data support the use of HUCPVCs as a more homogeneous source of stromal progenitors and potentially more useful for cell replacement therapy, or more likely, in better stimulating the endogenous recovery of injured tissue.…”

Alveolar Macrophages Are Critical for the Inhibition of Allergic Asthma by Mesenchymal Stromal Cells

“…The beneficial effects of BMMSC treatment in mouse models of cecal ligation and puncture-induced sepsis (43) and acute myocardial infarction (44) have been demonstrated to involve IL-10-producing M2 macrophages. Similarly, intrapulmonary delivery of mouse BMMSCs in a mouse model of endotoxin-induced acute lung injury was shown to induce increased production of IL-10, which could have been MSC derived or host derived (45).…”

In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence

“…25 MSC were grown until passage 4. The cells were cultured in Dulbecco's Modified Eagle's Medium low glucose, 2 mM of L-glutamine, 12.5% fetal bovine serum, and 100 u/mL of penicillin and streptomycin.…”