This study exploits transforming growth factor β (TGF-β) biology in RAI-refractory BRAF<sup>V600E</sup>-mutant papillary thyroid cancer (PTC) to selectively drive NIS transgene expression in engineered MSCs using a synthetic TGF-β1-inducible SMAD-responsive promoter (SMAD-NIS-MSCs) to reestablish RAI accumulation. Here, BRAF is linked to thyroid gland papillary carcinoma.