EGFR mRNA-Engineered Mesenchymal Stem Cells (MSCs) Demonstrate Radioresistance to Moderate Dose of Simulated Cosmic Radiation

Galactic cosmic ray (GCR) radiation is a major barrier to human space exploration beyond Earth’s magnetic field protection. Mesenchymal stem cells (MSCs) are found in all organs, and they play a critical role in repair and regeneration of tissue. We specifically use engineered bone marrow-derived MSCs as a model to evaluate the effect of radiation exposure during deep space travel and long-duration spaceflight. Epidermal growth factor receptor (EGFR) expression by certain types of cancers has been shown to induce radioresistance. In this study, we tested the feasibility of engineering MSCs to overexpress EGFR (eMSC-EGFR) and evaluated their capacity to tolerate and recover from exposure to x-ray exposure (1 – 20 Gy). Quantitative real-time PCR (qRT-PCR) and immunoblotting results have shown that EGFR was efficiently transfected into MSCs and EGFR protein was produced. eMSC-EGFR maintained characteristics of human MSCs as outlined by the International Society for Cell & Gene Therapy. Then, both eMSC-EGFR and naïve MSCs were exposed to various dose rates of x-ray irradiation to assess the potential radioprotective role of EGFR overexpression in MSCs. Analysis included post-irradiation evaluation of morphology, cell proliferation, tumorigenic potential, and DNA damage. eMSC-EGFR showed signs of radioresistance compared to naïve MSCs when assessing relative proliferation one week following exposure at doses of 1–8 Gy and significantly lower DNA damage content 24 hours after exposure to 4 Gy. We establish for the first time the feasibility of efficiently generating EGFR overexpressing MSCs as a model for enhancing the human body to tolerate and recover from moderate dose radiation injury in long-term manned space travel.