Paracrine Effect of Wnt11 Overexpressing Mesenchymal Stem Cells on Ischemic Injury

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In this study, we investigated whether Wnt11 enhances bone marrow‐derived mesenchymal stem cell (MSC) mediated cardioprotection via paracrine fashion following acute ischemia.MethodsMSCs were harvested from male rat bone marrow (BM) and transduced with Wnt11 (MSCWnt11). An acute myocardial infarction (MI) model in rats was developed by ligation of the left anterior descending coronary artery (LAD). MSCWnt11 were transplanted into the peri‐infarct region following acute MI. To mimic ischemic injury, cultured cardiomyocytes (CM) isolated from neonatal ventricles were exposed to hypoxia.ResultsELISA studies indicated that the release of Wnt11 (3.45‐fold) as well as transforming growth factor‐β2 (TGFβ2) (1.5‐fold) was significantly increased from MSCWnt11 compared to transduced control MSC (MSCNull). Hypoxia induced apoptosis and cell death was significantly reduced when CM were co‐cultured with MSCWnt11 in a dual chamber system. The cell protection mediated by MSCWnt11 was mimicked by treating CM with conditioned medium (CdM) from MSCWnt11 and abrogated by Wnt11‐ and TGFβ2‐neutralizing antibodies. Furthermore, animals receiving MSCWnt11 showed a significant improvement in cardiac contractile function as assessed by echocardiography. Infarct size measured from infarcted hearts was reduced from 44.6 ± 4.1% in control to 30.1 ± 3.0% in treated hearts (p < 0.05). Similarly, apoptosis of cardiomyocytes evaluated by TUNEL staining was reduced from 9.9 ± 0.71% in control group to 5.30 ± 0.35% in treated group (p < 0.05).ConclusionsTransplantation of MSCWnt11 improved cardiac function. The release of Wnt11 and other factors from MSCWnt11 transplanted in the infarcted left ventricle is more likely responsible for protection of CM at risk. This work was supported by National Institutes of Health grants: HL083236, HL105176 (M.X.) and HL087246 (M.A.).