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DOI: 10.1148/radiol.2381041668
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(Radiology 2006;238:200-210.)
© RSNA, 2006

Molecular Imaging

MR Evaluation of the Glomerular Homing of Magnetically Labeled Mesenchymal Stem Cells in a Rat Model of Nephropathy1

Olivier Hauger, MD, PhD, Emma E. Frost, PhD, Ruud van Heeswijk, BS, Colette Deminière, MD, R. Xue, PhD, Yahsou Delmas, MD, Christian Combe, MD, PhD, Chrit T. W. Moonen, PhD, Nicolas Grenier, MD and Jeff W. M. Bulte, PhD

1 From the Department of Radiology and Radiological Sciences (O.H., E.E.F., R.v.H., R.X., J.W.M.B.) and Institute for Cell Engineering (O.H., E.E.F., J.W.M.B.), Johns Hopkins University School of Medicine, Baltimore, Md; Department of Molecular and Functional Imaging, ERT CNRS/Université Victor Segalen-Bordeaux 2, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France (O.H., C.T.W.M., N.G.); and Anatomic Pathology Laboratory (C.D.) and Department of Nephrology (Y.D., C.C.), Hôpital Pellegrin, CHU Bordeaux, Bordeaux, France. Received October 1, 2004; revision requested November 25; revision received January 28, 2005; final version accepted February 25. O.H. supported by NIH RO1 NS 045062, Société Française de Radiologie, Institut National de la Santé et de la Recherche Médicale, and Fondation de France. Address correspondence to O.H. (e-mail: olivier.hauger{at}chu-bordeaux.fr).

Purpose: To assess renal glomerular homing of intravenously injected superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) at in vivo and ex vivo magnetic resonance (MR) imaging in an experimental rat model of mesangiolysis.

Materials and Methods: Animal procedures were performed in accordance with protocols approved by Institutional Animal Care and Use Committee. Fourteen rats were divided into two groups: one pathologic (n = 10), with persistent mesangiolysis following simultaneous injection of OX-7 monoclonal antibody and puromycin aminonucleoside in which 107 SPIO- and DiI-labeled MSCs were injected, and one control (n = 4). In vivo and ex vivo MR imaging examinations were performed with 4.7- and 9.4-T spectrometers, respectively, and T2*-weighted sequences. In vivo signal intensity variations were measured in the liver and kidney before and 6 days after MSC injection. Intrarenal signal intensity variations were correlated with histopathologic data by means of colocalization of DiI fluorescence, {alpha}-actin, and Prussian blue stain–positive cells. Histologic differences between the glomerular homing of MSCs in different kidney portions were correlated to the areas of MR signal intensity decrease with nonparametric statistical tests.

Results: On in vivo images, signal intensity measurements of pathologic kidneys following MSC injection did not show any signal intensity decrease (P = .7), whereas a 34% ± 14 (mean ± standard deviation) signal intensity decrease was observed in the liver (P < .01), where a substantial number of labeled cells were trapped. On ex vivo images, pathologic kidneys showed focal cortical (glomerular) areas of signal intensity loss, which was absent in controls. The areas of low signal intensity correlated well with {alpha}-actin and Prussian blue stain– and DiI-positive areas (P < .01), which indicates that MSCs specifically home to injured tissue. No MSCs were detected in the kidneys of control animals.

Conclusion: Intravenously injected MSCs specifically home to focal areas of glomerular damage and can be detected at ex vivo MR imaging.

© RSNA, 2006




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