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

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. (c) RSNA, 2006.