1. Human mesenchymal stem cells enhance the systemic effects of radiotherapy
- Author
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Beatriz Irene Fernández, José Mariano Ruiz de Almodóvar, Francisco Javier Oliver, Francisco O'Valle, María Carmen Ruiz-Ruiz, Virgínea de Araújo Farias, Ana M. Santos, Damián Guirado, J.J. López-Peñalver, Ana Nieto, Carmen Ruiz de Almodovar, Ana Guerra-Librero, Thomas Schmidt, Borja Alonso Lerma, [de Araújo Farias,V, O'Valle,F, Lerma,BA, López-Peñalver,JJ, Nieto,A, Santos,A, Fernández,BI, Guerra-Librero,A, Ruiz-Ruiz,MC, Ruiz de Almodóvar,JM] Instituto Universitario de Investigación en Biopatología y Medicina Regenerativa, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain. [de Araújo Farias,V, Oliver,FJ] Instituto de Parasitología y Biomedicina 'López Neyra', Consejo Superior de Investigaciones Científicas, Granada, Spain. [Ruiz de Almodóvar,C] Biochemistry Center, University of Heidelberg, Heidelberg, Germany. [López-Peñalver,JJ] Unidad de radiología experimental, Centro de Instrumentación Científica, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain. [Nieto,A] Unidad de Experimentación Animal, Centro de Instrumentación Científica, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain. [Santos,A] Unidad de Microscopia, Centro de Instrumentación Científica, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain. [Ruiz-Ruiz,MC] Departamento de Bioquímica y Biología Molecular III e Inmunología, IBIMER, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain. [Guirado,D, Ruiz de Almodóvar,JM] Hospital Universitario San Cecilio, Granada, Spain. [Schmidt,T] Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany., and This work was supported by Ministerio de Economía y Competividad, MINECO: SAF2012-40011-C02-02 to JMRdA, and MINECO SAF2012-40011-CO2-01 to F.J.O and CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico - Brasil.
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Técnicas para inmunoenzimas ,Ratones ,medicine.medical_treatment ,Mesenchymal cells ,Apoptosis ,Mice, SCID ,Células tumorales cultivadas ,Radioisótopos de cesio ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Immunoenzyme Techniques ,Bystander effect ,Mice ,Trasplante de células madre mesenquimatosas ,Mice, Inbred NOD ,Organisms::Eukaryota::Animals [Medical Subject Headings] ,Tumor Cells, Cultured ,Cytotoxic T cell ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Drug Evaluation, Preclinical::Drug Screening Assays, Antitumor::Xenograft Model Antitumor Assays [Medical Subject Headings] ,Melanoma ,Radiosensitizers ,Cancer ,mesenchymal cells ,Reverse Transcriptase Polymerase Chain Reaction ,Anatomy::Cells::Cells, Cultured::Tumor Cells, Cultured [Medical Subject Headings] ,Humanos ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoenzyme Techniques [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Reverse Transcriptase Polymerase Chain Reaction [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, SCID [Medical Subject Headings] ,Oncology ,Cesium Radioisotopes ,radiosensitizers ,Research Paper ,Western Blotting ,Blotting, Western ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Mesenchymal Stem Cell Transplantation [Medical Subject Headings] ,Mesenchymal Stem Cell Transplantation ,Real-Time Polymerase Chain Reaction ,Ratones SCID ,Células del estroma mesenquimatoso ,medicine ,Animals ,Humans ,cancer ,Anatomy::Cells::Connective Tissue Cells::Stromal Cells::Mesenchymal Stromal Cells [Medical Subject Headings] ,RNA, Messenger ,Radiosensitivity ,Chemicals and Drugs::Inorganic Chemicals::Isotopes::Cesium Isotopes::Cesium Radioisotopes [Medical Subject Headings] ,Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation [Medical Subject Headings] ,radiotherapy ,Cell Proliferation ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] ,Reacción en cadena en tiempo real de la polimerasa ,Reacción en cadena de la polimerasa de transcriptasa inversa ,Radiotherapy ,Cell growth ,business.industry ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Real-Time Polymerase Chain Reaction [Medical Subject Headings] ,Mesenchymal stem cell ,Proliferación de la célula ,Mesenchymal Stem Cells ,Bystander Effect ,medicine.disease ,Xenograft Model Antitumor Assays ,Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings] ,Radiation therapy ,Gamma Rays ,Animales ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Electrophoresis::Blotting, Western [Medical Subject Headings] ,Cancer research ,business ,Ensayos antitumor por modelo de xenoinjerto - Abstract
Journal 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. Yes
- Published
- 2015
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