Resveratrol Significantly Attenuates Cell Mediated Immune Rejection against Xenogenic Bovine Pericardium

Abstract

Resveratrol is a bioactive phenol shown to reduce T cell activation through inhibition of mTOR pathways. Recent studies show cell-mediated immune reactions cause structural valve deterioration (SVD) in xenograft valves. Thus, tissue-engineered heart valves (TEHV) with decellularized bovine pericardium have been developed to reduce the immune response. Our study examines whether resveratrol could further decrease the immune rejection against xenogenic bovine pericardium. Human peripheral blood mononuclear cells (PBMC) were isolated and resuspended in RPMI 1640 complete medium containing 10% human serum. The cells were further split into resveratrol (50μM/ml) and a vehicle group containing ethanol (50μM/ml) and cultured overnight in a 37C incubator. 2ml of the complete medium from each group containing 1 × 10^6 PBMC cells were then aliquoted into a cell culturing plate with each well containing either native bovine pericardium, decellularized bovine pericardium, allograft pericardium, autograft pericardium, or no pericardium. The exposed culture media were then collected for ELISA analysis after 1 and 3 days. Tumor necrosis factor-a (TNF-a), chiefly produced by macrophages in cell-mediated immunity, was measured. Resveratrol-treated cells showed a significant reduction in all of the tissue exposure types in comparison to vehicle-treated controls at both 1 and 3 days (n=4, P<0.02). Additionally, both vehicle control and resveratrol-treated groups at each time points generated the highest TNF-a concentration with native bovine pericardium exposure followed by the decellularized bovine pericardium, autograft pericardium, allograft pericardium, and no tissue. Resveratrol significantly decreases cell-mediated immune rejection against xenogenic bovine pericardium exposures. Therefore, resveratrol may serve as adjuvant therapy in TEHV replacements to further decrease the xenogenic immune reaction shown to cause SVD.