Abstract
We aimed to identify a suitable method for long-term monitoring of the migration and proliferation of mesenchymal stromal cells in stroke models of rats using ferritin transgene expression by magnetic resonance imaging (MRI). Bone marrow mesenchymal stromal cells (BMSCs) were transduced with a lentivirus containing a shuttle plasmid (pCDH-CMV-MCS-EF1-copGFP) carrying the ferritin heavy chain 1 (Fth1) gene. Ferritin expression in stromal cells was evaluated with western blotting and immunofluorescent staining. The iron uptake of Fth1-BMSCs was measured with Prussian blue staining. Following surgical introduction of middle cerebral artery occlusion, Fth1-BMSCs and superparamagnetic iron oxide- (SPIO-) labeled BMSCs were injected through the internal jugular vein. The imaging and signal intensities were monitored by diffusion-weighted imaging (DWI), T2-weighted imaging (T2WI), and susceptibility-weighted imaging (SWI) in vitro and in vivo. Pathology was performed for comparison. We observed that the MRI signal intensity of SPIO-BMSCs gradually reduced over time. Fth1-BMSCs showed the same signal intensity between 10 and 60 days. SWI showed hypointense lesions in the SPIO-BMSC (traceable for 30 d) and Fth1-BMSC groups. T2WI was not sensitive enough to trace Fth1-BMSCs. After transplantation, Prussian blue-stained cells were observed around the infarction area and in the infarction center in both transplantation models. Fth1-BMSCs transplanted for treating focal cerebral infarction were safe, reliable, and traceable by MRI. Fth1 labeling was more stable and suitable than SPIO labeling for long-term tracking. SWI was more sensitive than T2W1 and suitable as the optimal MRI-tracking sequence.
Highlights
Magnetic resonance imaging (MRI) is an important tool for cellular imaging as it can be used for clinical diagnostics
We showed that though we chose a high dose of Superparamagnetic iron oxide (SPIO) (6 × 104/ml) [18], the T2 relaxation time became progressively shorter during in vivo MRI tracking of superparamagnetic iron oxide- (SPIO-)Bone marrow mesenchymal stromal cells (BMSCs) implanted in the rat cerebral infarcted area probably because of cell mitosis leading to a decrease in the SPIO concentration with each division [8] and because of macrophage phagocytosis, which clears necrotic cells, including SPIO-labeled cells
The existing technique was too insensitive for tracing low concentrations of iron (SPIO), which affected and limited long-term observation of the biological behavior of BMSCs. erefore, we used BMSCs transfected with the ferritin heavy chain 1 (Fth1) gene using a lentivirus. e Fth1-BMSCs were transplanted to treat focal cerebral infarction induced in rats, and the sensitivity and 60 d (a)
Summary
Magnetic resonance imaging (MRI) is an important tool for cellular imaging as it can be used for clinical diagnostics. The fate of transplanted BMSCs in live animals is still poorly understood [2,3,4]. Us, a noninvasive, real-time, sensitive, and clinically applicable method for tracking transplanted BMSCs and monitoring their behavior in live animals would be useful. Superparamagnetic iron oxide (SPIO) has been used in several studies for tracking BMSCs in vitro and in vivo [1, 5, 6]. The hypointense MRI signal generated by these particles is not sustainable over a long time because the iron oxide nanoparticles are diluted with each cell division. BMSCs labeled with SPIO may not be a suitable method for long-term tracking of Contrast Media & Molecular Imaging
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
