Tracking of systemically administered mononuclear cells in the ischemic brain by high-field magnetic resonance
Albrecht Stroh1, Claus Zimmer, Nikos Werner
1Department of Radiology, Charité-Universitaetsmedizin Berlin, Schumannstrasse 20-21, 10117 Berlin, Germany. astroh@stanford.edu
Abstract:
This study was designed to track systemically administered mononuclear cells (MNCs) in the ischemic mouse brain using 7 T magnetic resonance imaging (MRI). Splenectomized wild-type mice were subjected to brain ischemia by 30 or 60 min filamentous occlusion of the middle cerebral artery (MCAo) and reperfusion. Spleen-derived MNCs were labeled with very small superparamagnetic iron-oxide particles (VSOP) and transfused into recipient mice 30 min, 8 h, or 24 h after MCAo via the tail vein. High-resolution MRI sequences were designed to monitor the dynamics of brain ischemia and to observe the migration and engraftment of transfused cells into the ischemic brain. T2*-weighted (gradient-echo) hypointense signal changes became apparent at 24-48 h after transfusion, were typically associated with the ischemic lesion border, and could be followed up to 5 weeks after the insult. Such presumed MNC-associated signal changes in MRI were confirmed by histochemical detection of iron (Prussian blue staining) and detection of constitutively expressed green fluorescent protein (GFP) in a subset of animals transfused with MNCs derived from GFP transgenic mice. Taken together, our results demonstrate that brain engraftment of systemically administered mononuclear cells can be visualized non-invasively over time and space using high-resolution MRI.
Insights
Researchers visualized systemically administered mononuclear cells (MNCs) in ischemic mouse brains using high-resolution magnetic resonance imaging (MRI). This non-invasive technique tracks cell migration and engraftment in the brain over time.
Area of Science:
- Neuroscience
- Medical Imaging
- Cell Biology
Background:
- Ischemic stroke remains a leading cause of disability, necessitating effective cell-based therapies.
- Tracking the fate of transplanted cells in the brain is crucial for evaluating therapeutic efficacy.
- Current methods for cell tracking are often invasive or lack long-term resolution.
Purpose of the Study:
- To develop and validate a non-invasive method for tracking systemically administered mononuclear cells (MNCs) in the ischemic mouse brain.
- To visualize the migration and engraftment dynamics of spleen-derived MNCs following middle cerebral artery occlusion (MCAo).
- To assess the feasibility of using high-resolution 7 Tesla (7T) MRI for monitoring cell behavior in vivo.
Main Methods:
- Induction of transient focal cerebral ischemia in splenectomized wild-type mice via middle cerebral artery occlusion (MCAo).
- Labeling of spleen-derived MNCs with very small superparamagnetic iron-oxide particles (VSOP) for MRI detection.
- Intravenous transfusion of labeled MNCs at different time points (30 min, 8 h, 24 h) post-MCAo.
- High-resolution 7T MRI acquisition to monitor ischemic lesion evolution and cell distribution.
- Histochemical validation using Prussian blue staining for iron and green fluorescent protein (GFP) detection.
Main Results:
- T2*-weighted hypointense MRI signals, indicative of iron-labeled MNCs, appeared at the ischemic lesion border 24-48 hours post-transfusion.
- These signal changes persisted for up to 5 weeks, demonstrating long-term engraftment.
- MRI findings were corroborated by Prussian blue staining and GFP expression in validated experiments.
- The study successfully visualized the non-invasive, spatiotemporal dynamics of cell engraftment.
Conclusions:
- High-resolution 7T MRI is a powerful tool for non-invasively visualizing the brain engraftment of systemically administered MNCs.
- This technique allows for real-time monitoring of cell migration and distribution in the ischemic brain.
- The findings support the potential of MRI-guided cell tracking for optimizing cell-based stroke therapies.
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