Fas inhibition of hypoxic mesenchymal stem cells for myocardial regeneration

Abstract

The use of mesenchymal stem cells (MSCs) as a therapy for myocardial disease is limited by poor viability of the transplanted cells. Reactive oxygen species (ROS) are generated in ischemic surroundings after myocardial infarction. Ischemic heart generated Fas ligand (FasL). FasL belongs to the TNF family that induces apoptosis in target cells binding Fas. This study aimed to determine if Fas-FasL complex mediated the death of MSCs in the ischemic heart. Expression levels of FasL were detected in a myocardial ischemia-reperfusion injury model. Expression of Fas was significantly increased in H2O2-treated MSCs in vitro. Survival of FasL-treated MSCs was decreased in H2O2-treatment compared to non-treated cells. When Fas was blocked using a Fas recombinant Fc chimera (Fas/Fc), caspase-8 and caspase-3 levels were lower than in FasL-treated MSCs. Increased survival was observed in Fas/Fc-treated MSCs compared to FasL-treated cells. These results indicate that Fas-Fas L complex interferes with the survival of MSCs and confirm a major role for the Fas-Fas L cytotoxic pathway in cardiac infarction.