MR evaluation of the glomerular homing of magnetically labeled mesenchymal stem cells in a rat model of nephropathy.
OBJECTIVE
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.


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 10(7) 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.


CONCLUSIONS
Intravenously injected MSCs specifically home to focal areas of glomerular damage and can be detected at ex vivo MR imaging.
Hauger
Olivier
O
Department of Radiology and Radiological Sciences, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. oliver.hauger@chu-bordeaux.fr
Frost
Emma E
EE
van Heeswijk
Ruud
R
Deminière
Colette
C
Xue
R
R
Delmas
Yahsou
Y
Combe
Christian
C
Moonen
Chrit T W
CT
Grenier
Nicolas
N
Bulte
Jeff W M
JW
D000818:Animals; D018929:Cell Culture Techniques; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007501:Iron; D007674:Kidney Diseases / Q000473:pathology / Q000628:therapy*; D007678:Kidney Glomerulus / Q000166:cytology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D010087:Oxides; D051381:Rats; D011917:Rats, Inbred Lew; D013194:Staining and Labeling
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide