Uso del transportador de NA/I (NIS) endógeno vehiculizado por células troncales y exosomas para terapia y diagnóstico del cáncer.

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Abstract

The sodium/iodide symporter (NIS) has become a therapeutic tool of great interest because of the capacity to allow the accumulation of certain ions on the NIS expressing cells. That ability gives NIS a dual function, as a diagnostic tool and/or as an antitumoral therapy. Nevertheless, it is necessary to find an adequate vehicle to transport that symporter to the specific target area. The main objective of this doctoral thesis is the development and optimization of innovative therapies based on the endogenous NIS expression for cancer treatment. Having that in mind, we postulated that human placenta-derived mesenchymal stem cells (hPMSCs) and their exosomes could be stablished as potential therapeutic vehicles thanks to their ability to migrate specifically to tumors and the possibility to express endogenous NIS. On the one hand, we were able to demonstrate that hPMSCs and their exosomes have endogenous expression of functional NIS. Furthermore, their expression is strong enough to track it in vivo and to cause a significant reduction in tumor growth in preclinic models when the radio-isotope 131I is administered. On the other hand, human maternal milk was considered as an alternative source of exosomes, knowing that NIS is highly expressed in the lactating mammary gland during breastfeeding. The characterization of human maternal milk exosomes shows that they express functional NIS and that the expression is strong enough to monitor those vesicles in vivo, they have a natural tropism for tumoral areas and they potentiate the therapeutic effect of the administration of 131I. In conclusion, the therapies that we have developed based on the endogenous NIS expression have great potential for cancer treatment in human patients. Suggestingthat in a near future the real effect of those therapies might be evaluated in the clinical practice.