A Comparative Study of Mesenchymal Stem Cell-Derived Extracellular Vesicles’ Local and Systemic Dose-Dependent Administration in Rat Spinal Cord Injury

SIMPLE SUMMARY: Spinal cord injury is a serious neurological condition that causes severe disability. The proposed solution of this problem is a cell-free therapy based on using microvesicles derived from stem cells (as an alternative to these cells, to achieve greater safety) intended for neuroregeneration. It was shown that, in the experimental groups with the use of microvesicles, the indicator of motor activity was higher than in the control ones. The best results were found in the group with intravenous administration of microvesicles in comparison with local administration (spinal cord area), where the recovery rate of motor function increased by more than two times compared to the control group. ABSTRACT: Spinal cord injury (SCI) is a serious neurological condition that causes severe disability. One of the approaches to overcoming the complications of SCI is stem cell-derived extracellular vesicle (EV) therapy. In this research, we performed a comparative evaluation of rat spinal cord post-traumatic regeneration efficacy using different methods of mesenchymal stem cell-derived EV transplantation (local vs. systemic) followed by evaluation of their minimal therapeutic dose. The results suggested that MSC-EV therapy could improve locomotor activity over 60 days after the SCI, showing a dose-dependent effect on the recovery of spinal cord motor pathways. We also established the possibility of maintaining a population of mature oligodendrocytes by MSC-EVs. It was observed that in the spinal cord injury area, intravenous transplantation of MSC-EVs showed more pronounced therapeutic effects compared to the treatment of fibrin matrix-encapsulated MSC-EVs.