Abstract 3905: MSCs Wnt11 Derived Paracrine Factors Are Critical to the Repair of Infarcted Myocardium

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Genetically engineered MSCs have been shown to serve as an effective vehicle for the delivery of protective proteins. We hypothesized that Wnt11 enhanced MSCs induced cardioprotection of ischemic myocardium via paracrine effect. We have successfully transfected Wnt11 into MSCs. Method: Conditioned medium (con-M) was obtained from various MSCs which were exposed to normoxia or hypoxia for 24 hours and was concentrated 100 times by ultrafiltration. Con-M (50μl) was injected into the border zone of infarcted myocardium immediately after rat underwent left anterior descending coronary artery (LAD) occlusion. Cultured cardiomyocytes (CM) were also treated with Con-M before cells were exposed to hypoxia. Result: A marked improvement in cardiac function was observed in the con-M from MSCs Wnt11 compared to the con-M from MSCs GFP (Table 1 ). Microarray analysis revealed that Wnt11 was 204 fold higher in MSCs Wnt11 than that in MSCs GFP . Moreover, many growth factors and cytokines were upregulated when MSCs Wnt11 were exposed to hypoxia for 24 hours (e.g. BMP4, 1.64; FGF1, 1.61 and TGFμ2, 2.21 fold higher than that in MSCs GFP , respectively; all p<0.05). Con-M significantly improved the survival of CM as expressed by an increased intake of MTT when CM were exposed to hypoxia. Neutralizing antibodies, including anti-Wnt11 (6 and 12 μg/ml) (Fig. 1 ), anti-BMP4 (3μg/ml), anti-FGF-1 (6μg/ml) and anti-TGFβ-2 (12μg/ml), abrogated the protection of CM induced by con-M, especially anti-FGF-1 (Fig. 2 ). It is concluded that MSCs Wnt11 protect cardiomyocytes by releasing cytoprotective factors in their environment. Table 1. Effects of condition medium on cardiac function Figure 1. Anti-Wnt11 antibody increased CM injury and abrogated the protective effect of conditioned medium against hypoxic damage. N = 4 in each group Figure 2. Neutralizing antibodies abolished the CM protection on cultured CM. #, p<0.05 vs normal control; *, p<0.05 vs hypoxia; †, p<0.05 vs Con-M-MSC GFP , ‡, p<0.05 vs Con-M-MSC Wnt11 respectively.