RT Journal Article T1 Human mesenchymal stem cells enhance the systemic effects of radiotherapy. A1 de Araújo Farias, Virgínea A1 O'Valle, Francisco A1 Lerma, Borja Alonso A1 Ruiz de Almodóvar, Carmen A1 López-Peñalver, Jesús J A1 Nieto, Ana A1 Santos, Ana A1 Fernández, Beatriz Irene A1 Guerra-Librero, Ana A1 Ruiz-Ruiz, María Carmen A1 Guirado, Damián A1 Schmidt, Thomas A1 Oliver, Francisco Javier A1 Ruiz de Almodóvar, José Mariano K1 Radiotherapy K1 Bystander effect K1 Mesenchymal cells K1 Cancer K1 Radiosensitizers K1 Western Blotting K1 Proliferación de la célula K1 Radioisótopos de cesio K1 Humanos K1 Técnicas para inmunoenzimas K1 Trasplante de células madre mesenquimatosas K1 Células del estroma mesenquimatoso K1 Ratones K1 Ratones SCID K1 Reacción en cadena en tiempo real de la polimerasa K1 Reacción en cadena de la polimerasa de transcriptasa inversa K1 Células tumorales cultivadas K1 Ensayos antitumor por modelo de xenoinjerto K1 Animales AB The outcome of radiotherapy treatment might be further improved by a better understanding of individual variations in tumor radiosensitivity and normal tissue reactions, including the bystander effect. For many tumors, however, a definitive cure cannot be achieved, despite the availablity of more and more effective cancer treatments. Therefore, any improvement in the efficacy of radiotherapy will undoubtedly benefit a significant number of patients. Many experimental studies measure a bystander component of tumor cell death after radiotherapy, which highlights the importance of confirming these observations in a preclinical situation. Mesenchymal stem cells (MSCs) have been investigated for use in the treatment of cancers as they are able to both preferentially home onto tumors and become incorporated into their stroma. This process increases after radiation therapy. In our study we show that in vitro MSCs, when activated with a low dose of radiation, are a source of anti-tumor cytokines that decrease the proliferative activity of tumor cells, producing a potent cytotoxic synergistic effect on tumor cells. In vivo administration of unirradiated mesenchymal cells together with radiation leads to an increased efficacy of radiotherapy, thus leading to an enhancement of short and long range bystander effects on primary-irradiated tumors and distant-non-irradiated tumors. Our experiments indicate an increased cell loss rate and the decrease in the tumor cell proliferation activity as the major mechanisms underlying the delayed tumor growth and are a strong indicator of the synergistic effect between RT and MSC when they are applied together for tumor treatment in this model. PB Impact Journals YR 2015 FD 2015-10-13 LK http://hdl.handle.net/10668/2566 UL http://hdl.handle.net/10668/2566 LA en NO de Araújo Farias V, O'Valle F, Lerma BA, Ruiz de Almodóvar C, López-Peñalver JJ, Nieto A, et al. Human mesenchymal stem cells enhance the systemic effects of radiotherapy. Oncotarget. 2015 ; 6(31):31164-80 NO Journal Article; Research Support, Non-U.S. Gov't; DS RISalud RD Apr 10, 2025