Dynamic MRI of the Mesenchymal Stem Cells Distribution during Intravenous Transplantation in a Rat Model of Ischemic Stroke

Abstract

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.

Mesenchymal stem cell‐derived extracellular vesicles for metabolic syndrome therapy: Assessing efficacy with nuclear magnetic resonance spectroscopy

“…The distribution of EVs was effectively monitored through MRI imaging, facilitated by the utilisation of superparamagnetic iron oxide (SPIO) nanoparticles coated with polyhistidine tags to label the MSC‐EVs. In vivo MRI imaging not only reveals the widespread presence of EVs in the body following the disease but also unveils their specific localisation in humans, thus offering invaluable insights for future research endeavours 51 …”

“…T2 weighted imaging allowed the researchers to monitor glial precursor cells at the described time intervals and to obtain quite new data about their homing to inflamed endothelium. MRI protocol can be a powerful tool in the evaluation of stem cell distribution and homing after intravenous administration and can be successfully applied in the personalised cell therapy translational studies 51. Beyond MSCs, noninvasive in vivo imaging techniques hold the exciting promise of effectively tracking administered EVs' delivery, uptake, and fate over time.…”