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Microglia used as vehicles for both inducible thymidine kinase gene therapy and MRI contrast agents for glioma therapy

hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorRIBOT, Emeline Julie
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorBOUZIER-SORE, Anne-Karine
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorBOUCHAUD, Véronique
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorMIRAUX, Sylvain
hal.structure.identifierInstitut de Chimie de la Matière Condensée de Bordeaux [ICMCB]
dc.contributor.authorDELVILLE, Marie-Hélène
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorFRANCONI, Jean-Michel
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorVOISIN, Pierre
dc.date.issued2007
dc.identifier.issn0929-1903
dc.description.abstractEnMicroglia are phagocytic cells that are chemoattracted by brain tumors and can represent up to 70% of the tumor cell population. To get insight into gene therapy against glioma, we decided to take advantage of those microglia properties and to use those cells as vehicles to transport simultaneously a suicide gene (under the control of a heat-sensitive promoter) and contrast agents to localize them by magnetic resonance imaging before applying any therapeutic treatment. Thymidine kinase (TK) expression and its functionality after gancyclovir administration were investigated. After the heat shock (44°C and 20 min), TK was expressed in 50% of the cells. However, after gancyclovir treatment, 90% of the cells died by apoptosis, showing an important bystander effect. Then, the cells were incubated with new lanthanide contrast agents to check both their potential toxicity and their MR properties. Results indicate that the nanoparticles did not induce any cell toxicity and yield a hypersignal on MR images at 4.7 T. These in vitro experiments indicate that microglia are good candidates as vectors in gene therapy against brain tumors. Finally, microglia containing gadolinium-grafted nanoparticles were injected in the close vicinity of C6 tumor, in a mouse. The hyperintensive signal obtained on in vivo images as well as its retention time show the potential of the novel contrast agents for cellular imaging.
dc.language.isoen
dc.publisherNature Publishing Group
dc.subject.enMicroglia
dc.subject.enHSP70 promoter
dc.subject.enTK/GCV system
dc.subject.enRhodamine-grafted nanoparticles
dc.subject.enT1-contrast agent
dc.subject.enMRI
dc.title.enMicroglia used as vehicles for both inducible thymidine kinase gene therapy and MRI contrast agents for glioma therapy
dc.typeArticle de revue
dc.identifier.doi10.1038/sj.cgt.7701060
dc.subject.halChimie/Matériaux
dc.subject.halSciences du Vivant [q-bio]/Cancer
bordeaux.journalCancer Gene Therapy
bordeaux.page724-737
bordeaux.volume14
bordeaux.issue8
bordeaux.peerReviewedoui
hal.identifierhal-00267022
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-00267022v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Cancer%20Gene%20Therapy&rft.date=2007&rft.volume=14&rft.issue=8&rft.spage=724-737&rft.epage=724-737&rft.eissn=0929-1903&rft.issn=0929-1903&rft.au=RIBOT,%20Emeline%20Julie&BOUZIER-SORE,%20Anne-Karine&BOUCHAUD,%20V%C3%A9ronique&MIRAUX,%20Sylvain&DELVILLE,%20Marie-H%C3%A9l%C3%A8ne&rft.genre=article


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