A Comparative Study of Mesenchymal Stem Cell-Derived Extracellular Vesicles’ Local and Systemic Dose-Dependent Administration in Rat Spinal Cord Injury
Alexander Kostennikov, Ilyas Kabdesh, Davran Sabirov, Anna Timofeeva, Alexander Rogozhin, Ilya Shulman, Albert A. Rizvanov, Yana Mukhamedshina
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.