Dynamic MRI of the Mesenchymal Stem Cells Distribution during Intravenous Transplantation in a Rat Model of Ischemic Stroke
Elvira A. Cherkashova,
Daria D. Namestnikova,
Ilya L. Gubskiy,
Veronica A. Revkova,
Kirill K. Sukhinich,
Pavel A. Melnikov,
Maxim A. Abakumov,
Galina D. Savina,
Vladimir P. Chekhonin,
Leonid V. Gubsky,
Konstantin N. Yarygin
Affiliations
Elvira A. Cherkashova
Department of Neurology, Neurosurgery and Medical Genetics, Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation, 117977 Moscow, Russia
Daria D. Namestnikova
Department of Neurology, Neurosurgery and Medical Genetics, Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation, 117977 Moscow, Russia
Ilya L. Gubskiy
Department of Neurology, Neurosurgery and Medical Genetics, Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation, 117977 Moscow, Russia
Veronica A. Revkova
Cell Technology Laboratory, Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies of the Federal Medical Biological Agency of Russian Federation, 115682 Moscow, Russia
Kirill K. Sukhinich
Laboratory of Cell Biology, Orekhovich Institute of Biomedical Chemistry of the Russian Academy of Sciences, 119121 Moscow, Russia
Pavel A. Melnikov
Department of Fundamental and Applied Neurobiology, Serbsky Federal Medical Research Centre of Psychiatry and Narcology of the Ministry of Healthcare of Russian Federation, 119034 Moscow, Russia
Maxim A. Abakumov
Department of Neurology, Neurosurgery and Medical Genetics, Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation, 117977 Moscow, Russia
Galina D. Savina
Department of General Pathology and Pathophysiology, Russian Medical Academy of Continuous Professional Education, 125284 Moscow, Russia
Vladimir P. Chekhonin
Department of Neurology, Neurosurgery and Medical Genetics, Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation, 117977 Moscow, Russia
Leonid V. Gubsky
Department of Neurology, Neurosurgery and Medical Genetics, Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation, 117977 Moscow, Russia
Konstantin N. Yarygin
Laboratory of Cell Biology, Orekhovich Institute of Biomedical Chemistry of the Russian Academy of Sciences, 119121 Moscow, Russia
Systemic transplantation of mesenchymal stem cells (MSCs) is a promising approach for the treatment of ischemia-associated disorders, including stroke. However, exact mechanisms underlying its beneficial effects are still debated. In this respect, studies of the transplanted cells distribution and homing are indispensable. We proposed an MRI protocol which allowed us to estimate the dynamic distribution of single superparamagnetic iron oxide labeled MSCs in live ischemic rat brain during intravenous transplantation after the transient middle cerebral artery occlusion. Additionally, we evaluated therapeutic efficacy of cell therapy in this rat stroke model. According to the dynamic MRI data, limited numbers of MSCs accumulated diffusely in the brain vessels starting at the 7th minute from the onset of infusion, reached its maximum by 29 min, and gradually eliminated from cerebral circulation during 24 h. Despite low numbers of cells entering brain blood flow and their short-term engraftment, MSCs transplantation induced long lasting improvement of the neurological deficit, but without acceleration of the stroke volume reduction compared to the control animals during 14 post-transplantation days. Taken together, these findings indicate that MSCs convey their positive action by triggering certain paracrine mechanisms or cell–cell interactions or invoking direct long-lasting effects on brain vessels.
