Korean J Radiol.  2009 Jun;10(3):277-284. 10.3348/kjr.2009.10.3.277.

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

• Jung SI
• Kim SH
• Kim HC
• Son KR
• Chung SY
• Moon WK
• Kim HS
• Choi JS
• Moon MH
• Sung CK

• KMID: 1779455
• DOI: http://doi.org/10.3348/kjr.2009.10.3.277

Abstract

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.

Keyword

Mesenchymal stem cell; Superparamagnetic iron oxide, MR; Kidney, ischemia

MeSH Terms

Animals
Disease Models, Animal
Ischemia/*diagnosis/*therapy
Kidney/blood supply/pathology
Kidney Diseases/*therapy
Magnetic Resonance Imaging/*methods
Male
Mesenchymal Stem Cell Transplantation/*methods
Mesenchymal Stem Cells/*pathology
Rats
Rats, Sprague-Dawley

Figure

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  Fig. 1 Left renal angiography after lodging in left renal artery with microcatheter. Left renal angiography shows sluggish left renal flow (arrow) after lodging for 40 minutes.

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  Fig. 2 Electron micrograph of superparamagnetic iron oxide labeled mesenchymal stem cells (original magnification, ×4,800). There are multiple endosomal vesicles containing superparamagnetic iron oxide particles (arrows) seen in cytoplasm of mesenchymal stem cells.

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  Fig. 3 Cell proliferation and viability of superparamagnetic iron oxide labeled mesenchymal stem cells. Any significant difference in number of cells was not observed between control cells and superparamagnetic iron oxide labeled cells for concentrations up to 125 µg/ml for cell proliferation (A) and cell viability (B). Data are shown as means ± standard deviation.

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  Fig. 4 T2*-weighted MR images before (A), 2 hours (B), 15 hours (C), 30 hours (D) and 72 hours (E) after injection of labeled mesenchymal stem cells. Left Ischemic kidney shows distinct decreased signal intensity (arrows) in cortex (B). However, signal intensity decrease shows progressive fading in C (arrows), D and E.

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  Fig. 5 Time course of signal intensity decrease on T2*-weighted image. Graph shows that signal intensity change on T2*-weighted image in renal cortex and medulla decreases with time after injection of labeled mesenchymal stem cells. Difference for signal intensity change was prominent at two hours in renal cortex and medulla for ischemic kidney (LT) and control kidney (RT). Data are shown as means ± standard deviation.

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  Fig. 6 Micrograph of histological specimen of ischemic kidney obtained at two hours after superparamagnetic iron oxide labeled mesenchymal stem cells injection (original magnification, ×200). Arrows indicate Prussian blue stain-positive particles in glomeruli and tubules of renal cortex.

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  Fig. 7 Time course of number of Prussian blue staining-positive cells per high-power field. Graph shows number of Prussian blue stain-positive cells in renal cortex and medulla after labeled mesenchymal stem cells injection as function of time. At two hours after injection, sharp decrease in number of cells is observed in renal cortex and medulla of ischemic kidney (LT). Gradual decrease in number of particles is observed in renal cortex and medulla of control kidney (RT). Data are shown as means ± standard deviation.

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