Journal
MOLECULAR THERAPY
Volume 19, Issue 9, Pages 1704-1713Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mt.2011.93
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Funding
- Deutsche Forschungsgemeinschaft, Bonn, Germany [SFB 824]
- Wilhelm-Sander-Stiftung [2008.037.1]
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Due to its dual role as reporter and therapy gene, the sodium iodide symporter (NIS) allows noninvasive imaging of functional NIS expression by I-123-scintigraphy or I-124-PET imaging before the application of a therapeutic dose of I-131. NIS expression provides a novel mechanism for the evaluation of mesenchymal stem cells (MSCs) as gene delivery vehicles for tumor therapy. In the current study, we stably transfected bone marrow-derived CD34(-) MSCs with NIS cDNA (NIS-MSC), which revealed high levels of functional NIS protein expression. In mixed populations of NIS-MSCs and hepatocellular cancer (HCC) cells, clonogenic assays showed a 55% reduction of HCC cell survival after I-131 application. We then investigated body distribution of NIS-MSCs by I-123-scintigraphy and I-124-PET imaging following intravenous (i.v.) injection of NIS-MSCs in a HCC xenograft mouse model demonstrating active MSC recruitment into the tumor stroma which was confirmed by immunohistochemistry and ex vivo gamma-counter analysis. Three cycles of systemic MSC-mediated NIS gene delivery followed by I-131 application resulted in a significant delay in tumor growth. Our results demonstrate tumor-specific accumulation and therapeutic efficacy of radioiodine after MSC-mediated NIS gene delivery in HCC tumors, opening the prospect of NIS-mediated radionuclide therapy of metastatic cancer using MSCs as gene delivery vehicles.
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