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Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain.

ABSTRACT: In vivo tracking of transplanted mesenchymal stem cells (MSCs) migration and homing is vital for understanding the mechanisms of beneficial effects of MSCs transplantation in animal models of diseases and in clinical trials. Transplanted cells can be labeled with superparamagnetic iron oxide (SPIO) particles and visualized in vivo using a number of iron sensitive MRI techniques. However, the applicability of those techniques for SPIO-labeled MSCs tracking in live brain has not been sufficiently investigated. The goal of this study was to estimate the efficiency of various MRI techniques of SPIO-labeled cell tracing in the brain. To achieve that goal, the precision and specificity of T2WI, T2*WI and SWI (Susceptibility-Weighted Imaging) techniques of SPIO-labeled MSCs tracing in vitro and in live rat brain were for the first time compared in the same experiment. We have shown that SWI presents the most sensitive pulse sequence for SPIO-labeled MSCs MR visualization. After intracerebral administration due to limitations caused by local micro-hemorrhages the visualization threshold was 102 cells, while after intra-arterial transplantation SWI permitted detection of several cells or even single cells. There is just one publication claiming detection of individual SPIO-labeled MSCs in live brain, while the other state much lower sensitivity, describe detection of different cell types or high resolution tracing of MSCs in other tissues. This study confirms the possibility of single cell tracing in live brain and outlines the necessary conditions. SWI is a method convenient for the detection of single SPIO labeled MSCs and small groups of SPIO labeled MSCs in brain tissue and can be appropriate for monitoring migration and homing of transplanted cells in basic and translational neuroscience.

SUBMITTER: Namestnikova D

PROVIDER: S-EPMC5648235 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Endothelial progenitor cells (EPCs) have been discovered to be relevant to the prognosis of cardiovascular diseases. Previous research has demonstrated that EPCs serve vital roles in the occurrence and development of atherosclerosis. Significant improvements have been made in MRI technology and in the experimental use of EPCs for therapeutic angiogenesis and vascular repair. Nevertheless, the migratory, adhesive, proliferative and angiogenic properties of EPCs remain unknown. The aims of the present study were to investigate the potential of using non?invasive monitoring with ultrasmall superparamagnetic iron oxide nanoparticle (USPION)?labeled endothelial progenitor cells (EPCs) after transplantation, and to assess the treatment outcomes in an atherosclerotic rabbit model. EPCs derived from rabbit peripheral blood samples were labeled with USPION?poly?l?lysine (USPION?PLL). The morphology, proliferation, adhesive ability and labeling efficiency of the EPCs were determined by optical and electron microscopy. Moreover, biological activity was assessed by flow cytometry. In addition, T2?weighted image fast spin?echo MRI was used to detect cell labeling. USPION content in the labeled EPCs was determined by Prussian blue staining and scanning electron microscopy. Rabbit atherosclerosis model was established using a high?fat diet. USPION?labeled EPCs were transplanted into rabbits, and in vivo MRI was performed 1 and 7 days after transplantation. It was found that EPCs cultured on Matrigel formed capillary?like structures, and expressed the surface markers CD133, CD31, CD34 and vascular endothelial growth factor receptor 2 (VEGFR2). The optimal USPION concentration was 32 µg/ml, as determined by adhesion and proliferation assays. It was identified that USPION?PLL nanoparticles were 10?20 nm in diameter. Histopathological analysis results indicated that 1 day after transplantation of the labeled EPCs, blue?stained granules were observed in the intima of vascular lesions in rabbit models after Prussian blue staining. Therefore, the present results suggest that USPION?labeled EPCs may play a role in repairing endothelial injury and preventing atherosclerosis in vivo.

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Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain.

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