title: Spatiotemporal control of gene expression in bone-marrow derived cells of the tumor microenvironment induced by MRI guided focused ultrasound.
abstract: The tumor microenvironment is an interesting target for anticancer therapies but modifying this compartment is challenging. Here, we demonstrate the feasibility of a gene therapy strategy that combined targeting to bone marrow-derived tumor microenvironment using genetically modified bone-marrow derived cells and control of transgene expression by local hyperthermia through a thermo-inducible promoter. Chimera were obtained by engraftment of bone marrow from transgenic mice expressing reporter genes under transcriptional control of heat shock promoter and inoculated sub-cutaneously with tumors cells. Heat shocks were applied at the tumor site using a water bath or magnetic resonance guided high intensity focused ultrasound device. Reporter gene expression was followed by bioluminescence and fluorescence imaging and immunohistochemistry. Bone marrow-derived cells expressing reporter genes were identified to be mainly tumor-associated macrophages. We thus provide the proof of concept for a gene therapy strategy that allows for spatiotemporal control of transgenes expression by macrophages targeted to the tumor microenvironment.
authors: Laboratoire d'Imagerie Moléculaire et Fonctionnelle (IMF), CNRS/UMR 5231, Université de Bordeaux, Bordeaux, France.|Institut de Bio-Imagerie (IBIO), CNRS/UMS 3428, Université de Bordeaux, Bordeaux, France.
authors: Pierre-Yves
authors: PY
authors: Fortin
authors: Laboratoire d'Imagerie Moléculaire et Fonctionnelle (IMF), CNRS/UMR 5231, Université de Bordeaux, Bordeaux, France.
authors: Matthieu
authors: M
authors: Lepetit-Coiffé
authors: Laboratoire d'Imagerie Moléculaire et Fonctionnelle (IMF), CNRS/UMR 5231, Université de Bordeaux, Bordeaux, France.|Institut de Bio-Imagerie (IBIO), CNRS/UMS 3428, Université de Bordeaux, Bordeaux, France.
authors: Coralie
authors: C
authors: Genevois
authors: Laboratoire d'Imagerie Moléculaire et Fonctionnelle (IMF), CNRS/UMR 5231, Université de Bordeaux, Bordeaux, France.
authors: Christelle
authors: C
authors: Debeissat
authors: Laboratoire d'Imagerie Moléculaire et Fonctionnelle (IMF), CNRS/UMR 5231, Université de Bordeaux, Bordeaux, France.
authors: Bruno
authors: B
authors: Quesson
authors: Laboratoire d'Imagerie Moléculaire et Fonctionnelle (IMF), CNRS/UMR 5231, Université de Bordeaux, Bordeaux, France.
authors: Chrit T W
authors: CT
authors: Moonen
authors: Centre de Résonance Magnétique des Systèmes Biologiques (RMSB), CNRS/UMR 5536, Université de Bordeaux, Bordeaux, France.
authors: Jan Pieter
authors: JP
authors: Konsman
authors: Laboratoire d'Imagerie Moléculaire et Fonctionnelle (IMF), CNRS/UMR 5231, Université de Bordeaux, Bordeaux, France.|Centre de Résonance Magnétique des Systèmes Biologiques (RMSB), CNRS/UMR 5536, Université de Bordeaux, Bordeaux, France.
authors: Franck
authors: F
authors: Couillaud
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000000981:diagnostic imaging* / Q000473:pathology*; D002277:Carcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D005838:Genotype; D006358:Hot Temperature; D006979:Hyperthermia, Induced; D007150:Immunohistochemistry; D008027:Light; D008264:Macrophages / Q000166:cytology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D010641:Phenotype; D011401:Promoter Regions, Genetic; D059016:Tumor Microenvironment; D014463:Ultrasonography / Q000379:methods
keywords: cancer; gene therapy; molecular imaging