Dynamic Tracking of Injected Mesenchymal Stem Cells after Myocardial Infarction in Rats: A Serial 7T MRI Study
Xiuyu Chen1, Minjie Lu1, Ning Ma2
1Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
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 × 10(6)/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.
Insights
Micron-sized particles of iron oxide (MPIO) are unreliable for tracking mesenchymal stem cells (MSCs) long-term after heart attack. However, MSCs still improve cardiac function and reduce damage despite poor cell retention.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Biomedical Imaging
Background:
- Myocardial infarction (MI) leads to adverse cardiac remodeling.
- Mesenchymal stem cells (MSCs) show therapeutic potential for MI.
- Tracking transplanted MSCs in vivo is crucial for understanding their efficacy.
Purpose of the Study:
- To evaluate micron-sized particles of iron oxide (MPIO) for tracking MPIO-labeled MSCs in a rat MI model using 7T MRI.
- To assess the impact of MSC transplantation on cardiac function and remodeling post-MI.
Main Methods:
- MSCs dual-labeled with MPIO and CM-DiI were injected into the infarct periphery of rats 7 days post-MI.
- 7T MRI was used to dynamically assess stem cell location, signal intensity, and cardiac function at multiple time points.
- Histological analysis and real-time PCR were performed to evaluate cell fate, inflammation, and tissue repair.
Main Results:
- MPIOs caused observable hypointensities on T2*-weighted MRI, indicating their presence.
- MSCs transplantation moderated left ventricular remodeling and improved cardiac function.
- Most iron-positive cells were identified as macrophages, and MSC survival decreased significantly over time.
- MSC treatment increased capillary density and reduced cardiomyocyte apoptosis and fibrosis in the peri-infarct region.
Conclusions:
- MPIOs are not a reliable marker for long-term in vivo tracking of MSC engraftment.
- Despite limited cell retention, MSCs demonstrate significant therapeutic benefits in mitigating adverse cardiac remodeling after MI.
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