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REAL-TIME MRI OF MESENCHYMAL STEM CELL DISTRIBUTION IN RAT BRAIN AFTER INTRA-ARTERIAL AND INTRAVENOUS TRANSPLANTATION IN EXPERIMENTAL STROKE
Abstract
Background and Aims
Transplantation of mesenchymal stem cells (MSC) is a promising approach for ischemic stroke treatment. The investigation of cell fate after transplantation could be one of the key factors on the way to understand the mechanisms of therapeutic effects of transplanted cells. The aim of this work was to study precise distribution of MSC in ischemic rat brain starting from the first pass through cerebral vascularity after intra-arterial (IA) and intravenous (IV) administration using real-time MRI.
Methods
Human placenta MSC were transplanted IA (5x105cells,n=25) or IV (2x106cells,n=25) into male Wistar rats 24h after 90min MCAO. Administration of SPIO labeled cells were performed inside 7Т-MRI scanner, T2*WI with 1min resolution for IA and SWI with 7min resolution for IV administration were performed. MRI data was confirmed by histology.
Results
After IA administration within first 5min MSC were detected in the periphery of the infarct core and brain stem, 15min later in the infarct core and contralateral hemisphere, after 30min the number of cells in all described regions reached their maximum. MSC were localized inside cerebral vessels in close contact with their walls. In case of IV administration MSC were visualized in both hemispheres only 15min after injection. MSC could no longer be detected in the brain 72h after IA and 24h after IV infusion.
Conclusions
The obtained data on MSC distribution and homing confirms the paracrine mechanism of action of transplanted cells after stroke. This work was financially supported by the grant of the Ministry of Science and Higher Education of Russian Federation №075-15-2020-792 (Unique identifier RF----190220X0031).