In vivo MRI tracking of iron oxide nanoparticle-labeled human mesenchymal stem cells in limb ischemia

Abstract

Background: Stem cell transplantation has been investigated for repairing damaged tissues in various injury models. Monitoring the safety and fate of transplanted cells using noninvasive methods is important to advance this technique into clinical applications. Methods: In this study, lower-limb ischemia models were generated in nude mice by femoral artery ligation. As negative-contrast agents, positively charged magnetic iron oxide nanoparticles (aminopropyltriethoxysilane-coated Fe 2 O 3 ) were investigated in terms of in vitro labeling efficiency, effects on human mesenchymal stromal cell (hMSC) proliferation, and in vivo magnetic resonance imaging (MRI) visualization. Ultimately, the mice were sacrificed for histological analysis three weeks after transplantation. Results: With efficient labeling, aminopropyltriethoxysilane-modified magnetic iron oxide nanoparticles (APTS-MNPs) did not significantly affect hMSC proliferation. In vivo, APTS-MNP-labeled hMSCs could be monitored by clinical 3 Tesla MRI for at least three weeks. Histological examination detected numerous migrated Prussian blue-positive cells, which was consistent with the magnetic resonance images. Some migrated Prussian blue-positive cells were positive for mature endothelial cell markers of von Willebrand factor and anti-human proliferating cell nuclear antigen. In the test groups, Prussian blue-positive nanoparticles, which could not be found in other organs, were detected in the spleen. Conclusion: APTS-MNPs could efficiently label hMSCs, and clinical 3 Tesla MRI could monitor the labeled stem cells in vivo, which may provide a new approach for the in vivo monitoring of implanted cells.

PET Cell Tracking Using 18F-FLT is Not Limited by Local Reuptake of Free Radiotracer

“…It is important to understand cell retention in order to understand their mechanism of action, to develop techniques which help retain cells at the site of injury and to clarify optimal dosing regimens. There are different imaging modalities which can be employed in cardiovascular cell tracking studies 1 including; magnetic resonance imaging 2 3 , optical 4 , ultrasound 5 , single-photon emission computed tomography (SPECT) 6 7 and positron emission tomography (PET) 8 9 . With PET, cells can either be directly labelled, transplanted and tracked; or indirectly tracked post-transplantation using PET reporter genes 10 .…”