In vivo magnetic resonance imaging of iron oxide-labeled, intravenous-injected mesenchymal stem cells in kidneys of rabbits with acute ischemic kidney injury: detection and monitoring at 1.5 T

Abstract

Background: Acute kidney injury (AKI) is one of the most important causes of mortality and morbidity worldwide. Mesenchymal stem cells (MSCs) can be used for stem cell-based therapy containing AKI. Magnetic resonance imaging (MRI) is an ideal mean for stem cells tracking by labeling with superparamagnetic iron oxide (SPIO). Therefore, using the iron oxide-labeled mesenchymal stem cells (MSC) to treat the AKI and evaluating migration, distribution, and homing of cells by MRI is an ideal method for cell therapy and cell tracking in vivo. Methods: In vitro, the MSCs were labeled with 25 μg/mL for 24 h, and test the labeled efficiency and cells viability. In vitro experiments, magnetic resonance imaging (MRI) measurement of non-labeled and SPIO-labeled MSCs (SPIO-MSCs) was performed in correlation to detectable cells concentrations and detectable time windows. In vivo experiments, MRI evaluation was performed before and after ischemic/reperfusion AKI (N = 14) and intravenous injection of 5 × 10⁵ SPIO-MSCs (N = 10), PBS (N = 6) up to 8 days using a clinical 1.5 T scanner. Signal intensity of kidneys were measured and tested for statistical significance (unpaired Student’s t-test, p < 0.05) in comparison histology (hematoxylin and eosin [H&E], Prussian blue). Results: In vitro, MSCs can be labeled with the SPIO without affecting the viability and labeling efficiency. SPIO-MSCs showed a reduction of signal intensity at T2WI and T2*WI, 5 × 10⁴cells/mL, SPIO-MSCs were the minimum imaging cells concentration using a 1.5 T MR in vitro. In vivo, SPIO-MSCs administration resulted in a T2*WI signal intensity decrease in renal medulla caused by SPIO-MSCs accumulation in contrast to control groups (p < 0.05) up to day 3 after transplantation, but T2*WI low signal intensity region of the renal medulla revealed an decrease at day 5, and no significant differences between SPIO-MSCs and control animals at day 8. Conclusion: Our data demonstrate that in vitro and in vivo, cell-tracking and monitoring of kidney distribution of intravenous injected SPIO-MSCs after AKI is feasible in MRI at 1.5 T.

• Acute kidney injury
• iron oxide particles
• magnetic resonance imaging
• mesenchymal stem cells

Acknowledgments

We are indebted to Xin Lei and Jing Li for their help with data collection. In addition, we are very grateful to Professor Jun Xie for their laboratory assistance for this manuscript and Ruifeng Liang for help with statistical analysis.

Declaration of interest

The authors declare that they have no competing interests.

This study was supported by grants from the National Natural Science Foundation of China (Grant number: 81371628) and Postdoctoral Science Foundation of China (Grant number: 2013M541206).

Supplementary material available online

Supplementary Figure 1.