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

PLoS One. 2017 Oct 19;12(10):e0186717. doi: 10.1371/journal.pone.0186717. eCollection 2017.

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.

MeSH terms

  • Animals
  • Cell Proliferation
  • Cell Survival
  • Cell Transplantation*
  • Corpus Striatum*
  • Ferric Compounds / chemistry*
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Mesenchymal Stem Cells / cytology*
  • Phantoms, Imaging
  • Rats

Substances

  • Ferric Compounds
  • ferric oxide

Grants and funding

Part of the work (labeling of hMSCs, immunocytochemistry, fluorescent, confocal and bright-field microscopy) was carried out within the framework of the Program for Basic Research of the State Academies of Sciences for 2013-2020, theme no. 0518-2014-0005; URL: www.fano.gov.ru. Isolation and characterization of hMSCs were supported with grant of Ministry of Education and Science of the Russian Federation agreement 14.621.21.0017, unique project ID RFMEFI62117X0017. MRI experiments were supported by grant no. 16-29-07116 from the Russian Foundation for Basic Research; URL: www.rfbr.ru. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.