TY - JOUR
T1 - MR evaluation of the glomerular homing of magnetically labeled mesenchymal stem cells in a rat model of nephropathy
AU - Hauger, Olivier
AU - Frost, Emma E.
AU - Van Heeswijk, Ruud
AU - Deminière, Colette
AU - Xue, R.
AU - Delmas, Yahsou
AU - Combe, Christian
AU - Moonen, Chrit T.W.
AU - Grenier, Nicolas
AU - Bulte, Jeff W.M.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/1
Y1 - 2006/1
N2 - 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, α-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 α-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.
AB - 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, α-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 α-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.
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U2 - 10.1148/radiol.2381041668
DO - 10.1148/radiol.2381041668
M3 - Article
C2 - 16373768
AN - SCOPUS:29444442414
SN - 0033-8419
VL - 238
SP - 200
EP - 210
JO - RADIOLOGY
JF - RADIOLOGY
IS - 1
ER -