Mesenchymal Stem Cells-derived Exosomes as Probable Triggers of Radiation-induced Heart Disease

Abstract Background: Radiation-induced heart disease have been reported, but the mechanisms remain unclear. Mesenchymal stem cells (MSCs), also resident in heart are highly susceptible to radiation. We examined the hypothesis that altered secretion of exosomes from MSCs as the triggers of radiation-induced heart disease. Methods: By exposing human placental tissue-derived MSCs to 5 Gy γ-rays, we will then isolate exosomes from the culture medium 48h later and use to evaluate the quantity and quality changes of exosomes from MSCs after radiation exposures. The biological effects of exosomes from irradiated MSCs on HUVEC and H9c2 cells were also examined. Results: Although the amount and size distribution of exosomes did not differ between the non-irradiated and irradiated MSCs, miRNA sequences indicated many up- or down-regulated miRNAs in irradiated MSCs-exosomes. In vitro experiments using HUVEC and H9c2 cells showed that irradiated MSCs-exosomes significantly decreased cell proliferation, but increased cell apoptosis and DNA damage. Moreover, irradiated MSCs-exosomes impaired the tube formation of HUVEC cells and induced calcium overload of H9c2 cells. Conclusions: Exosomes released from irradiated MSCs shows an altered miRNA profiling and harmful effect to damage heart cells, which provides new insight on the mechanism of radiation-related heart disease risks.