Using TGF-β1 Biology in Radioiodine Refractory Differentiated Thyroid Cancer to Re-establish Sodium Iodide Symporter Expression Using Engineered Mesenchymal Stem Cells as Therapy Vehicles.

Han, Yang; Koehler, Viktoria F; Nagarajah, James; Schmohl, Kathrin A; Stauss, Christina; Schwenk, Nathalie; Spellerberg, Rebekka; Kitzberger, Carolin; Kumbrink, Joerg; Zach, Christian; Steiger, Katja; Morris, John C; Weber, Wolfgang A; Bartenstein, Peter; Ziegler, Sibylle I; Nelson, Peter J; Spitzweg, Christine

doi:10.1016/j.ymthe.2025.10.033

journal article

Titel:: Using TGF-β1 Biology in Radioiodine Refractory Differentiated Thyroid Cancer to Re-establish Sodium Iodide Symporter Expression Using Engineered Mesenchymal Stem Cells as Therapy Vehicles.
Dokumenttyp:: Journal Article
Autor(en):: Han, Yang; Koehler, Viktoria F; Nagarajah, James; Schmohl, Kathrin A; Stauss, Christina; Schwenk, Nathalie; Spellerberg, Rebekka; Kitzberger, Carolin; Kumbrink, Joerg; Zach, Christian; Steiger, Katja; Morris, John C; Weber, Wolfgang A; Bartenstein, Peter; Ziegler, Sibylle I; Nelson, Peter J; Spitzweg, Christine
Abstract:: The sodium iodide symporter (NIS) mediates iodine uptake into thyroid follicular cells providing the basis for radioiodine imaging and therapy of differentiated thyroid cancer. Loss of functional NIS expression leads to radioiodine-refractory disease. Restoration of radioiodine uptake via NIS delivery into tumors using mesenchymal stem cells (MSCs) represents a therapeutic strategy for radioiodine-refractory differentiated thyroid cancer. This study exploits transforming growth factor-beta (TGF-β) biology in radioiodine-refractory BRAFV600E-mutant papillary thyroid cancer to selectively drive NIS transgene expression in engineered MSCs using a synthetic TGF-β1-inducible SMAD-responsive promoter (SMAD-NIS-MSCs) to reestablish radioiodine accumulation. 125I uptake assay confirmed stimulation of functional NIS expression in SMAD-NIS-MSCs through TGF-β1 released from BRAFV600E-mutant papillary thyroid cancer cell lines (BCPAP, K1) from co-culture or by incubation with tumor-conditioned medium. Chemotaxis assays showed directed chemotaxis of MSCs towards BCPAP- and K1-tumor-conditioned medium. SMAD-NIS-MSCs applied intravenously to mice harboring BCPAP or K1 xenografts followed by 123I-scintigraphy demonstrated tumor-specific MSC recruitment and radioiodine accumulation. Application of SMAD-NIS-MSCs followed by 131I demonstrated a significant delay in tumor growth with prolonged survival. We demonstrate re-establishment of NIS-mediated radioiodine therapy in radioiodine-refractory BRAFV600E-mutant papillary thyroid cancer tumors using MSC-mediated NIS gene delivery driven by their TGF-β1 biology. «
The sodium iodide symporter (NIS) mediates iodine uptake into thyroid follicular cells providing the basis for radioiodine imaging and therapy of differentiated thyroid cancer. Loss of functional NIS expression leads to radioiodine-refractory disease. Restoration of radioiodine uptake via NIS delivery into tumors using mesenchymal stem cells (MSCs) represents a therapeutic strategy for radioiodine-refractory differentiated thyroid cancer. This study exploits transforming growth factor-beta (TGF-... »
Zeitschriftentitel:: Mol Ther
Jahr:: 2025
Volltext / DOI:: doi:10.1016/j.ymthe.2025.10.033
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/41109953
Print-ISSN:: 1525-0016
TUM Einrichtung:: 602; Institut für Allgemeine Pathologie und Pathologische Anatomie (Dr. Mogler komm.); Klinik und Poliklinik für Nuklearmedizin (Prof. Weber)
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