scholarly journals Effective control of tumor growth through spatial and temporal control of theranostic sodium iodide symporter (NIS) gene expression using a heat-inducible gene promoter in engineered mesenchymal stem cells

Theranostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 4490-4506 ◽  
Author(s):  
Mariella Tutter ◽  
Christina Schug ◽  
Kathrin A. Schmohl ◽  
Sarah Urnauer ◽  
Nathalie Schwenk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Sodium Iodide ◽  
Gene Promoter ◽  
Effective Control ◽  
Sodium Iodide Symporter ◽  
Nis Gene ◽  
Inducible Gene

scholarly journals Taking Advantage of the TGFB1 Biology in Differentiated Thyroid Cancer to Stimulate Sodium Iodide Symporter (NIS)-Mediated Iodide Uptake in Engineered Mesenchymal Stem Cells

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1033-A1033
Author(s):  
Yang Han ◽  
Viktoria F Koehler ◽  
Nathalie Schwenk ◽  
Kathrin A Schmohl ◽  
Rebekka Spellerberg ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Nis Gene

Abstract The sodium iodide symporter (NIS) mediates the active transport of iodide into thyroid follicular cells, providing the basis for the use of radioiodide for diagnostic imaging and therapy of differentiated thyroid cancer and also non-thyroidal tumors after tumor-selective NIS gene transfer. Based on their excellent tumor-homing capacity, mesenchymal stem cells (MSCs) can be employed as tumor-selective NIS gene delivery vehicles. Transgenic expression of NIS in genetically engineered MSCs allows noninvasive imaging of functional NIS expression as well as therapeutic application of 131I. The use of promoters activated by tumor micromilieu-derived signals to drive NIS expression enhances selectivity and effectiveness, while limiting potential off-target effects. In this study we aimed to exploit the central role of transforming growth factor B1 (TGFB1) in tumor milieu-associated signaling using a TGFB1-inducible synthetic SMAD-responsive promoter to selectively drive NIS-transgene expression in engineered MSCs (SMAD-NIS-MSC) in the context of differentiated thyroid cancer based on the critical role of TGFB1 in the pathogenesis of radioiodine refractory differentiated thyroid cancer. To evaluate the TGFB1 expression in thyroid cancer cell lines, the TGFB1 concentration in conditioned medium (CM) from an array of established human papillary thyroid cancer (PTC) cell lines (BCPAP and K1) was measured by ELISA. BCPAP-CM showed a higher concentration of TGFB1, while a lower concentration was measured in K1-CM. Stimulation of SMAD-NIS-MSCs with PTC-CM showed a significant increase of NIS-mediated radioiodide-125 uptake in these MSCs in vitro. In addition, iodide uptake in SMAD-NIS-MSCs was significantly stimulated by co-culture with thyroid cancer cells. Cell migration assay was performed to validate the effect of PTC-CM in MSC recruitment. MSCs subjected to a gradient between tumor CM and serum free medium showed a directed chemotaxis towards CM with increased forward migration index (FMI) and center of mass (CoM). In a next step, based on the in vitro studies, SMAD-NIS-MSCs will be systemically applied via the tail vein to mice harboring subcutaneous PTC tumors and tumoral iodide uptake will be monitored by 123I-scintigraphy. Taken together, these data indicate the feasibility of commandeering TGF-β/SMAD signaling in the TGFB1-rich tumor environments of radioiodine refractory differentiated thyroid carcinomas to re-establish functional NIS expression using engineered mesenchymal stem cells as therapy vehicles.

scholarly journals Effect of thyroid statuses on sodium / iodide symporter (NIS) gene expression in the extrathyroidal tissues in mice

2010 ◽  
Vol 3 (1) ◽  
pp. 3 ◽  
Author(s):  
Md. Harun-Or-Rashid ◽  
Masato Asai ◽  
Xiao-yang Sun ◽  
Yoshitaka Hayashi ◽  
Junichi Sakamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Nis Gene

Sodium Iodide Symporter (NIS) Gene Expression in Human Placenta

Placenta ◽  
2001 ◽  
Vol 22 (2-3) ◽  
pp. 256-258 ◽  
Author(s):  
A.M Mitchell ◽  
S.W Manley ◽  
J.C Morris ◽  
K.A Powell ◽  
E.R Bergert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Placenta ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Nis Gene

In vitro monitoring of cardiomyogenic differentiation of mesenchymal stem cells using sodium iodide symporter gene

2012 ◽  
Vol 9 (6) ◽  
pp. 304-310 ◽  
Author(s):  
Min Hwan Kim ◽  
Yong Jin Lee ◽  
Kwang Il Kim ◽  
Tae Sup Lee ◽  
Kwang Sun Woo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Cardiomyogenic Differentiation

scholarly journals Sodium/Iodide Symporter (NIS) Gene Expression Is the Limiting Step for the Onset of Thyroid Function in the Human Fetus

2007 ◽  
Vol 92 (1) ◽  
pp. 70-76 ◽  
Author(s):  
Gabor Szinnai ◽  
Ludovic Lacroix ◽  
Aurore Carré ◽  
Fabien Guimiot ◽  
Monique Talbot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Function ◽  
Human Fetus ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Limiting Step ◽  
Nis Gene

scholarly journals Stromal Targeting of Sodium Iodide Symporter Using Mesenchymal Stem Cells Allows Enhanced Imaging and Therapy of Hepatocellular Carcinoma

2013 ◽  
Vol 24 (3) ◽  
pp. 306-316 ◽  
Author(s):  
Kerstin Knoop ◽  
Nathalie Schwenk ◽  
Patrick Dolp ◽  
Michael J. Willhauck ◽  
Christoph Zischek ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Enhanced Imaging
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