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In Vivo MR Tracking of Mesenchymal Stem Cells in Rat Liver after Intrasplenic Transplantation¹

¹ From the Laboratory of Molecular Imaging, Department of Radiology, Zhongda Hospital (S.J., G.J.T., H.L., F.C.), Laboratory of Molecular and Biomolecular Electronics (Y.Z.), and School of Basic Medical Science (A.Z.), Southeast University, 87 Ding Jia Qiao Road, Nanjing 210009, China; and Department of Radiology, University Hospitals, Catholic University of Leuven, Leuven, Belgium (F.C., Y.N.). Received July 26, 2006; revision requested September 27; revision received November 20; accepted December 20; final version accepted February 12, 2007. Supported by National Nature Science Foundation of China grant 30400116 and Natural Science Foundation of Jiangsu Province grant Bk2004068. Address correspondence to G.J.T. (e-mail: gjteng{at}vip.sina.com).

Purpose: To prospectively track in vivo in rats intrasplenically transplanted stem cells labeled with superparamagnetic particles by using magnetic resonance (MR) imaging.

Materials and Methods: The study was approved by the institutional Committee on Animal Research. Liver damage in 12 rats was induced with subcutaneous injection of carbon tetrachloride (CCl₄). Intrasplenic transplantation of 6 x 10⁶ rodent bone mesenchymal stem cells (BMSCs) with (n = 6) and without (n = 6) superparamagnetic particle Fe₂O₃-poly-L-lysine (PLL) labeling was performed via direct puncture. Cell labeling efficiency was assessed in vitro by using Prussian blue stain and an atomic absorption spectrometer. MR examinations were performed immediately before and 3 hours and 3, 7, and 14 days after transplantation. Liver-to-muscle contrast-to-noise ratios (CNRs) on T2*-weighted MR images obtained before and after injection were measured and correlated with histomorphologic studies. Statistical analyses were performed by using repeated-measures analysis of variance.

Results: Rat BMSCs could be effectively labeled with approximately 100% efficiency. Migration of transplanted labeled cells to the liver was successfully documented with in vivo MR imaging. CNRs on T₂*-weighted images decreased significantly in the liver 3 hours after injection of BMSCs (P < .05) and returned gradually to the level achieved without labeled cell injection in 14 days. Histologic analyses confirmed the presence of BMSCs in the liver. The labeled cells primarily localized in the sinusoids of periportal areas and the foci of CCl₄-induced liver damage. Quantitative analysis of Prussian blue-stained cells indicated gradual decrease of dye pigments from 3 hours to 3, 7, and 14 days after injection. No free iron particles were found in the interstitium or within hepatic microvessels.

Conclusion: The rat BMSCs could be efficiently labeled with Fe₂O₃-PLL and the relocation of the labeled cells to rat livers after intrasplenic transplantation could be depicted at in vivo MR imaging.

© RSNA, 2007