Red wine antioxidant resveratrol-modified cardiac stem cells regenerate infarcted myocardium

To study the efficiency of maintaining the reduced tissue environment via pre-treatment with natural antioxidant resveratrol in stem celltherapy, we pre-treated male Sprague-Dawley rats with resveratrol (2.5 mg/kg/day gavaged for 2 weeks). After occlusion of the left anteriordescending coronary artery (LAD), adult cardiac stem cells stably expressing EGFP were injected into the border zone of themyocardium. One week after the LAD occlusion, the cardiac reduced environment was confirmed in resveratrol-treated rat hearts by theenhanced expression of nuclear factor-E2-related factor-2 (Nrf2) and redox effector factor-1 (Ref-1). In concert, cardiac functionalparameters (left ventricular ejection fraction and fractional shortening) were significantly improved. The improvement of cardiac functionwas accompanied by the enhanced stem cell survival and proliferation as demonstrated by the expression of cell proliferationmarker Ki67 and differentiation of stem cells towards the regeneration of the myocardium as demonstrated by the enhanced expressionof EGFP 28 days after LAD occlusion in the resveratrol-treated hearts. Our results demonstrate that resveratrol maintained a reducedtissue environment by overexpressing Nrf2 and Ref-1 in rats resulting in an enhancement of the cardiac regeneration of the adult cardiacstem cells as demonstrated by increased cell survival and differentiation leading to cardiac function.