Abstract
Purpose. To track the fate of micron-sized particles of iron oxide (MPIO) labeled mesenchymal stem cells (MSCs) in vivo in a rat myocardial infarction model using 7T magnetic resonance imaging (MRI) scanner. Materials and Methods. Male MSCs (2 × 106/50 μL) dual-labeled with MPIO and CM-DiI were injected into the infarct periphery 7 days after myocardial infarction (MI). The control group received cell-free media injection. The temporal stem cell location, signal intensity, and cardiac function were dynamically assessed using a 7T MRI at 24 h before transplantation (baseline), 3 days, 2 weeks, and 4 weeks after transplantation, respectively. Results. MR hypointensities caused by MPIOs were observed on T2⁎-weighted images at all time points after MSCs injection. Cine-MRI showed that MSCs moderated progressive left ventricular remodeling. Double staining for iron and CD68 revealed that most of the iron-positive cells were CD68-positive macrophages. Real-time PCR for rat SRY gene showed the number of survival MSCs considerably decreased after transplantation. MSC-treated hearts had significantly increased capillary density in peri-infarct region and lower cardiomyocytes apoptosis and fibrosis formation. Conclusions. Iron particles are not a reliable marker for in vivo tracking the long-term fate of MSCs engraftment. Despite of poor cell retention, MSCs moderate left ventricular remodeling after MI.
Highlights
Stem cell-based therapy has been currently introduced as a potentially promising approach to treat myocardial infarction (MI) and heart failure
T2∗-weighted imaging is able to determine whether iron-labeled cells were successfully transplanted into the target sites of infarcted hearts as well as the initial cell retention, which is crucial for the following therapeutic effects on cardiac function and makes Magnetic resonance imaging (MRI) an potentially ideal monitoring imaging modality for tracking the fate of engrafted mesenchymal stem cells (MSCs)
Our preliminary study has revealed that MRI scanner with ultra-high magnetic field (7.0T) could accurately evaluate the cardiac function and morphology in MI models of rats whereas superparamagnetic iron oxide nanoparticles were unable to reliably track the fate of engrafted MSCs
Summary
Stem cell-based therapy has been currently introduced as a potentially promising approach to treat myocardial infarction (MI) and heart failure. Noticeable concerns have been raised and yet to be studied, such as the fate of transplanted cells and the underlying mechanisms of the functional benefits. Magnetic resonance imaging (MRI) is currently considered as a standard tool to evaluate the cardiac morphology and function due to its versatility, accuracy, and reproducibility and has been most frequently applied in the clinical trials [4,5,6,7,8]. T2∗-weighted imaging is able to determine whether iron-labeled cells were successfully transplanted into the target sites of infarcted hearts as well as the initial cell retention, which is crucial for the following therapeutic effects on cardiac function and makes MRI an potentially ideal monitoring imaging modality for tracking the fate of engrafted MSCs
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