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