7-T MRI tracking of mesenchymal stromal cells after lung injection in a rat model

Abstract

Background: Mesenchymal stromal cells (MSCs) are able to migrate and engraft at sites of inflammation, injuries, and tumours, but little is known about their fate after local injection. The purpose of this study is to perform MSC tracking, combining in vivo 7-T magnetic resonance imaging (MRI) and histological assessment, following lung injection in a rat model. Methods: Five lungs were injected with ferumoxide-labelled MSCs and five with perfluorocarbon-labelled MSCs and underwent 7-T MRI. MRI acquisitions were recorded immediately (T0), at 24 h (T24) and/or 48 h (T48) after injection. For each rat, labelled cells were assessed in the main organs by MRI. Target organs were harvested under sterile conditions from rats sacrificed 0, 24, or 48 h after injection and fixed for histological analysis via confocal and structured illumination microscopy. Results: Ferumoxide-labelled MSCs were not detectable in the lungs, whereas they were not visible in the distant sites. Perfluorocarbon-labelled MSCs were seen in 5/5 injected lungs at T0, in 1/2 at T24, and in 1/3 at T48. The fluorine signal in the liver was seen in 3/5 at T0, in 1/2 at T24, and in 2/3 at T48. Post-mortem histology confirmed the presence of MSCs in the injected lung. Conclusions: Ferumoxide-labelled cells were not seen at distant sites; a linear decay of injected perfluorocarbon-labelled MSCs was observed at T0, T24, and T48 in the lung. In more than half of the experiments, perfluorocarbon-labelled MSCs scattering to the liver was observed, with a similar decay over time as observed in the lung.