In Vivo MR Imaging of Magnetically Labeled Mesenchymal Stem Cells in a Rat Model of Renal Ischemia

Objective: This study was designed to evaluate in vivo MR imaging for the depiction of intraarterially injected superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in an experimental rat model of renal ischemia. Materials and Methods: Left renal ischemia was induced in 12 male Sprague-Dawley rats by use of the catheter lodging method. In vivo MR signal intensity variations depicted on T2*-weighted sequences were evaluated in both the left and right kidneys prior to injection (n = 2), two hours (n = 4), 15 hours (n = 2), 30 hours (n = 2) and 72 hours (n = 2) after injection of SPIO-labeled MSCs in both kidneys. Signal intensity variations were correlated with the number of Prussian blue stain-positive cells as visualized in histological specimens. Results: In an in vivo study, it was determined that there was a significant difference in signal intensity variation for both the left and right cortex (40.8 +/- 4.12 and 26.4 +/- 7.92, respectively) and for both the left and right medulla (23.2 +/- 3.32 and 15.2 +/- 3.31, respectively) until two hours after injection (p < 0.05). In addition, signal intensity variation in the left renal cortex was well correlated with the number of Prussian blue stain-positive cells per high power field (r = 0.98, p < 0.05). Conclusion: Intraarterial injected SPIO-labeled MSCs in an experimental rat model of renal ischemia can be detected with the use of in vivo MR imaging immediately after injection.This study was partly supported by a grant from the Seoul Research and Business Development Program 10548 and by a grant (A062260) from the Innovative Research Institute for Cell Therapy, Republic of Korea.Ittrich H, 2007, J MAGN RESON IMAGING, V25, P1179, DOI 10.1002/jmri.20925Hauger O, 2006, RADIOLOGY, V238, P200, DOI 10.1148/radiol.2381041668Togel F, 2005, AM J PHYSIOL-RENAL, V289, pF31, DOI 10.1152/ajprenal.00007.2005Bos C, 2004, RADIOLOGY, V233, P781, DOI 10.1148/radiol.2333031714Bulte JWM, 2004, NMR BIOMED, V17, P484, DOI 10.1002/nbm.924Grove JE, 2004, STEM CELLS, V22, P487Herzog EL, 2003, BLOOD, V102, P3483, DOI 10.1182/blood-2003-05-1664Kalish H, 2003, MAGNET RESON MED, V50, P275, DOI 10.1002/mrm.10556Frank JA, 2003, RADIOLOGY, V228, P480, DOI 10.1148/radiol.2281020638Jo SK, 2003, KIDNEY INT, V64, P43Kale S, 2003, J CLIN INVEST, V112, P42, DOI 10.1172/JCI200317856Bulte JWM, 2003, MAGNET RESON MED, V50, P201, DOI 10.1002/mrm.10511Kraitchman DL, 2003, CIRCULATION, V107, P2290, DOI 10.1161/01.CIR.0000070931.62772.4EGupta S, 2002, KIDNEY INT, V62, P1285Krause DS, 2002, GENE THER, V9, P754Bulte JWM, 2001, NAT BIOTECHNOL, V19, P1141Lewin M, 2000, NAT BIOTECHNOL, V18, P410Kelly KJ, 2000, SEMIN NEPHROL, V20, P4Firbank MJ, 1999, PHYS MED BIOL, V44, pN261, DOI 10.1088/0031-9155/44/12/403Josephson L, 1999, BIOCONJUGATE CHEM, V10, P186Sutton TA, 1998, SEMIN NEPHROL, V18, P490Thadhani R, 1996, NEW ENGL J MED, V334, P1448SHANLEY PF, 1986, AM J PATHOL, V122, P462