de Araújo Farias, VirgíneaO'Valle, FranciscoLerma, Borja AlonsoRuiz de Almodóvar, CarmenLópez-Peñalver, Jesús JNieto, AnaSantos, AnaFernández, Beatriz IreneGuerra-Librero, AnaRuiz-Ruiz, María CarmenGuirado, DamiánSchmidt, ThomasOliver, Francisco JavierRuiz de Almodóvar, José Mariano2016-12-122016-12-122015-10-13de 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):31164-80http://hdl.handle.net/10668/2566Journal Article; Research Support, Non-U.S. Gov't;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.enRadiotherapyBystander effectMesenchymal cellsCancerRadiosensitizersWestern BlottingProliferación de la célulaRadioisótopos de cesioHumanosTécnicas para inmunoenzimasTrasplante de células madre mesenquimatosasCélulas del estroma mesenquimatosoRatonesRatones SCIDReacción en cadena en tiempo real de la polimerasaReacción en cadena de la polimerasa de transcriptasa inversaCélulas tumorales cultivadasEnsayos antitumor por modelo de xenoinjertoAnimalesMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::ApoptosisMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Electrophoresis::Blotting, WesternMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell ProliferationMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Isotopes::Cesium Isotopes::Cesium RadioisotopesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoenzyme TechniquesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Mesenchymal Stem Cell TransplantationMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Stromal Cells::Mesenchymal Stromal CellsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, SCIDMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Real-Time Polymerase Chain ReactionMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Reverse Transcriptase Polymerase Chain ReactionMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Tumor Cells, CulturedMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Drug Evaluation, Preclinical::Drug Screening Assays, Antitumor::Xenograft Model Antitumor AssaysMedical Subject Headings::Organisms::Eukaryota::Animalsresearch article26378036open access10.18632/oncotarget.52161949-2553PMC4741595