Abstract 3905: MSCsWnt11 Derived Paracrine Factors Are Critical to the Repair of Infarcted Myocardium
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 MSCsWnt11 compared to the con-M from MSCsGFP (Table 1⇓). Microarray analysis revealed that Wnt11 was 204 fold higher in MSCsWnt11 than that in MSCsGFP. Moreover, many growth factors and cytokines were upregulated when MSCsWnt11 were exposed to hypoxia for 24 hours (e.g. BMP4, 1.64; FGF1, 1.61 and TGFμ2, 2.21 fold higher than that in MSCsGFP, 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 MSCsWnt11 protect cardiomyocytes by releasing cytoprotective factors in their environment.