The Impact of Cerebral Perfusion on Mesenchymal Stem Cells Distribution after Intra-Arterial Transplantation: A Quantitative MR Study.

Ilya L Gubskiy,Maxim A Abakumov,Veronica A Revkova,Leonid V Gubsky,Konstantin N Yarygin,Daria D Namestnikova,Kirill K Sukhinich,Elvira A Cherkashova,Pavel A Melnikov,Mikhail M Beregov,Vladimir P Chekhonin

doi:10.3390/biomedicines10020353

Abstract

Intra-arterial (IA) mesenchymal stem cells (MSCs) transplantation providing targeted cell delivery to brain tissue is a promising approach to the treatment of neurological disorders, including stroke. Factors determining cell distribution after IA administration have not been fully elucidated. Their decoding may contribute to the improvement of a transplantation technique and facilitate translation of stroke cell therapy into clinical practice. The goal of this work was to quantitatively assess the impact of brain tissue perfusion on the distribution of IA transplanted MSCs in rat brains. We performed a selective MR-perfusion study with bolus IA injection of gadolinium-based contrast agent and subsequent IA transplantation of MSCs in intact rats and rats with experimental stroke and evaluated the correlation between different perfusion parameters and cell distribution estimated by susceptibility weighted imaging (SWI) immediately after cell transplantation. The obtained results revealed a certain correlation between the distribution of IA transplanted MSCs and brain perfusion in both intact rats and rats with experimental stroke with the coefficient of determination up to 30%. It can be concluded that the distribution of MSCs after IA injection can be partially predicted based on cerebral perfusion data, but other factors requiring further investigation also have a significant impact on the fate of transplanted cells.

Highlights

Transplantation of mesenchymal stem cells (MSCs) is a novel approach to the treatment of many severe neurological disorders causing irreversible damage of neural tissue, including traumatic brain injury, spinal cord injury, multiple sclerosis, neurodegenerative diseases, and stroke [1,2,3]
superparamagnetic iron oxide (SPIO)-labeled MSCs after transplantation can be visualized as hypointense spots on susceptibility weighted imaging (SWI), since the SPIO label reduces T2* relaxation time
magnetic resonance imaging (MRI) data of cells distribution were verified by histological examination: double cell labeling (SPIO-dragon green and PKH26) combined with immunohistochemical staining with antibodies against human mitochondria allowed detection of human MSCs in the rat brain sections and its subsequent comparison with MR-images

Summary

Introduction

Transplantation of mesenchymal stem cells (MSCs) is a novel approach to the treatment of many severe neurological disorders causing irreversible damage of neural tissue, including traumatic brain injury, spinal cord injury, multiple sclerosis, neurodegenerative diseases, and stroke [1,2,3]. According to the ClinicalTrials.gov site, five-phase I and II clinical trials focused on IA administration of MSCs or bone marrow mononuclear cells into patients with subacute or chronic ischemic stroke have been registered throughout the world and some of them have been already completed (reviewed in [4,11]). The published results of the clinical trials indicate that IA transplantation of cells is essentially safe in humans and can promote some neurological improvement after stroke. Further investigation and better understanding of the mechanisms of MSCs’ therapeutic effects, as well as the assessment of cell distribution and homing after transplantation may help to resolve these issues [5]

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