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Successful Mitigation of Radiation Injuries in Mice using Mesenchymal Stem Cells Genetically Modified to Secrete Extracellular Superoxide Dismutase

Weiwen Deng, Aly S. Abdel-Mageed, Robert H. Connors, Daniel W. Pietryga, Anthony J. Senagore, Troy A Giambernardi and Rick V. Hay

Oxidative stress is a major determinant for radiation-induced tissue injuries. We present a novel method that harnesses the power of migration of mesenchymal stem cells (MSCs) to radiation injured tissues and adenovirusmediated extracellular superoxide dismutase (ECSOD) gene therapy for oxidative stress. This report demonstrates for the first time that intravenous administration of MSCs genetically modified to secrete ECSOD at 24 hours after radiation exposure can improve survival from 10% to 52%, extend lifespan for 207 days, retard cataract formation for 39 days, and prevent carcinogenesis in mice. For proof-of-concept, we further demonstrate for the first time that human MSCs can be genetically modified with adenoviral vector to secrete high levels of biologically active ECSOD. Our findings suggest that mesenchymal stem cell-based antioxidant gene therapy has the potential for mitigation of radiation injuries in humans as a consequence of radiological and nuclear emergencies, space radiation exposure, and cancer radiotherapy toxicity.