Volume 24, Issue 10 p. 1361-1368
Research Article

In vivo MR tracking of therapeutic microglia to a human glioma model

Emeline J. Ribot

Corresponding Author

Emeline J. Ribot

Centre de Résonance Magnétique des Systèmes Biologiques, CNRS/Université V. Ségalen Bordeaux, Bordeaux, France

Centre de Résonance Magnétique des Systèmes Biologiques (RMSB), UMR 5536, CNRS/Université V. Segalen Bordeaux, 146 rue Léo Saignat, 33076 Bordeaux, FranceSearch for more papers by this author
Sylvain Miraux

Sylvain Miraux

Centre de Résonance Magnétique des Systèmes Biologiques, CNRS/Université V. Ségalen Bordeaux, Bordeaux, France

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Jan P. Konsman

Jan P. Konsman

PsychoNeuroImmunologie, Nutrition et Génétique, Université V. Ségalen Bordeaux, Bordeaux, France

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Véronique Bouchaud

Véronique Bouchaud

Centre de Résonance Magnétique des Systèmes Biologiques, CNRS/Université V. Ségalen Bordeaux, Bordeaux, France

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Line Pourtau

Line Pourtau

Centre de Résonance Magnétique des Systèmes Biologiques, CNRS/Université V. Ségalen Bordeaux, Bordeaux, France

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Marie-Hélène Delville

Marie-Hélène Delville

Institut de Chimie de la Matière Condensée de Bordeaux, Université Bordeaux 1, Pessac, France

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Jean-Michel Franconi

Jean-Michel Franconi

Centre de Résonance Magnétique des Systèmes Biologiques, CNRS/Université V. Ségalen Bordeaux, Bordeaux, France

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Eric Thiaudière

Eric Thiaudière

Centre de Résonance Magnétique des Systèmes Biologiques, CNRS/Université V. Ségalen Bordeaux, Bordeaux, France

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Pierre J. Voisin

Pierre J. Voisin

Centre de Résonance Magnétique des Systèmes Biologiques, CNRS/Université V. Ségalen Bordeaux, Bordeaux, France

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First published: 08 March 2011
Citations: 25

Abstract

A knowledge of the spatial localization of cell vehicles used in gene therapy against glioma is necessary before launching therapy. For this purpose, MRI cell tracking is performed by labeling the cell vehicles with contrast agents. In this context, the goal of this study was to follow noninvasively the chemoattraction of therapeutic microglial cells to a human glioma model before triggering therapy. Silica nanoparticles grafted with gadolinium were used to label microglia. These vehicles, expressing constitutively the thymidine kinase suicide gene fused to the green fluorescent protein gene, were injected intravenously into human glioma-bearing nude mice. MRI was performed at 4.7 T to track noninvasively microglial accumulation in the tumor. This was followed by microscopy on brain slices to assess the presence in the glioma of the contrast agents, microglia and fusion gene through the detection of silica nanoparticles grafted with tetramethyl rhodamine iso-thiocyanate, 3,3′-dioctadecyloxacarbocyanine perchlorate and green fluorescent protein fluorescence, respectively. Finally, gancyclovir was administered systemically to mice. Human microglia were detectable in living mice, with strong negative contrast on T2*-weighted MR images, at the periphery of the glioma only 24 h after systemic injection. The location of the dark dots was identical in MR microscopy images of the extracted brains at 9.4 T. Fluorescence microscopy confirmed the presence of the contrast agents, exogenous microglia and suicide gene in the intracranial tumor. In addition, gancyclovir treatment allowed an increase in mice survival time. This study validates the MR tracking of microglia to a glioma after systemic injection and their use in a therapeutic strategy against glioma. Copyright © 2011 John Wiley & Sons, Ltd.