Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci Arujo Farias, Virgínea de O'Valle Ravassa, Francisco Javier Serrano Saenz, Santiago Anderson, Per Olof Andrés, Eduardo López-Peñalver, Jesús Tovar Gálvez, María Isabel Nieto, Ana Santos, Ana Martín, Francisco Expósito, José Oliver, Javier Ruiz De Almodóvar Rivera, José Mariano Experimental radiotherapy Bystander effect Abscopal effect Mesenchymal stem cells Cell therapy Metastasis spread Proteomic analysis Annexin A1 Melanoma xenograft We have recently shown that radiotherapy may not only be a successful local and regional treatment but, when combined with MSCs, may also be a novel systemic cancer therapy. This study aimed to investigate the role of exosomes derived from irradiated MSCs in the delay of tumor growth and metastasis after treatment with MSC + radiotherapy (RT). The tumor cell loss rates found after treatment with the combination of MSC and RT and for exclusive RT, were: 44.4% % and 12,1%, respectively. Concomitant and adjuvant use of RT and MSC, increased the mice surviving time 22,5% in this group, with regard to the group of mice treated with exclusive RT and in a 45,3% respect control group. Moreover, the number of metastatic foci found in the internal organs of the mice treated with MSC + RT was 60% less than the mice group treated with RT alone. We reasoned that the exosome secreted by the MSC, could be implicated in tumor growth delay and metastasis control after treatment. Our results show that exosomes derived form MSCs, combined with radiotherapy, are determinant in the enhancement of radiation effects observed in the control of metastatic spread of melanoma cells and suggest that exosome-derived factors could be involved in the bystander, and abscopal effects found after treatment of the tumors with RT plus MSC. Radiotherapy itself may not be systemic, although it might contribute to a systemic effect when used in combination with mesenchymal stem cells owing the ability of irradiated MSCs-derived exosomes to increase the control of tumor growth and metastasis. 2019-11-18T10:08:26Z 2019-11-18T10:08:26Z 2019 journal article de Araujo Farias, V., O’Valle, F., Serrano-Saenz, S., Anderson, P., Andrés, E., López-Peñalver, J., ... & Expósito, J. (2018). Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci. Molecular cancer, 17(1), 122. http://hdl.handle.net/10481/57944 10.1186/s12943-018-0867-0 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España Springer Nature