Based on the role of TGF-β as a critical tumor milieu-associated signaling factor expressed in most solid tumors, we have previously demonstrated a robust therapeutic efficacy when using a TGF-β1-inducible synthetic SMAD-responsive promoter to selectively drive NIS-transgene expression in engineered MSCs (SMAD-NIS-MSC) within the tumor milieu. TGF-β is critically important in thyroid cancer, especially in the pathogenesis of BRAFV600E-positive radioiodine (RAI) refractory differentiated thyroid cancer. In this project, we are aiming to attack the tumor with its own weapons by commandeering the TGF-β biology underlying RAI refractory thyroid cancer to re-induce RAI accumulation in the tumor.