Abdelrhaman, Aly

Background Stem cells undergo significant death after transplantation, but the mechanisms underlying this deleterious response remain unclear. Increased oxidative stress has been shown to be present in states of hypoxia or cellular stress. Thus, we hypothesize that oxidative stress blockade would ameliorate the increased cell death when exposed to hypoxia. Methods Cardiac stem cells were exposed to hypoxic conditions in cell culture (1% O 2 for 24 hours). Oxidative status (by measuring reactive oxygen species‐ROS‐) and cell survival (by the MTT assay) were measured. In a separate group of cells, oxidative stress was blocked using a superoxide dismutase mimetic (Tempol, 1‐10µm/L). Results Hypoxia resulted in increased expression of the oxidative stress enzyme NAD(P)H oxidase (subfraction 47 phox ) and in the amount of ROS (increased in the conversion of dihydroethidium ‐DHE‐ and dichlorofluorescein ‐DCF‐) what led to a decrease in stem cell viability. Pre‐conditioning of stem cells with antioxidants (Tempol) decreased the amount of cellular ROS and improved stem cell survival. The increased expression of NAD(P)H p47 phox seen in hypoxia was unaltered by oxidative stress blockade. Conclusion Increased oxidative stress plays a role in the early cell death after hypoxia. Understanding of the mechanisms underlying the fate of stem cells will be critical for the advancement of the field of stem cell therapy.