The use of stem and progenitor cells to restore damaged organs and tissues, in particular, the central nervous system, is currently considered a most promising therapy in regenerative medicine. At the same time, another approach aimed at stimulating regeneration with the use of stem cells encapsulated into a biopolymer matrix and capable of creating a specific microenvironment for the implanted cells similar to the natural extracellular matrix is under active development. Here, we study effects of the application of adipose-derived mesenchymal stem cells (AD-MSCs) combined with a fibrin matrix on post-traumatic reactions in the spinal cord in rats. The AD-MSC application is found to exert a positive impact on the functional and structural recovery after spinal cord injury (SCI) that has been confirmed by the results of behavioral/electrophysiological and morphometric studies demonstrating reduced area of abnormal cavities and enhanced tissue retention in the site of injury. Immunohistochemical and real-time PCR analyses provide evidence that AD-MSC application decreases the GFAP expression in the area of SCI that might indicate the reduction of astroglial activation. Our results also demonstrate that AD-MSC application contributes to marked upregulation of PDGFβR and HSPA1b mRNA expression and decrease of Iba1 expression at the site of the central canal. Thus, the application of AD-MSCs combined with fibrin matrix at the site of SCI during the subacute period can stimulate important mechanisms of nervous tissue regeneration and should be further developed for clinical applications.

Here, we provide a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix, in small (rat) and large (pig) spinal cord injury (SCI) models during subacute period of spinal contusion. Results of behavioral, electrophysiological, and histological assessment as well as immunohistochemistry and real-time polymerase chain reaction analysis suggest that application of AD-MSCs combined with a fibrin matrix within the subacute period in rats (2 weeks after injury), provides significantly higher post-traumatic regeneration compared to a similar application of BM-MSCs or DP-MSCs. Within the rat model, use of AD-MSCs resulted in a marked change in: (1) restoration of locomotor activity and conduction along spinal axons; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of microglial and astroglial activation. The effect of an autologous application of AD-MSCs during the subacute period after spinal contusion was also confirmed in pigs (6 weeks after injury). Effects included: (1) partial restoration of the somatosensory spinal pathways; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of astroglial activation in dorsal root entry zone. However, pigs only partially replicated the findings observed in rats. Together, these results indicate application of AD-MSCs embedded in fibrin matrix at the site of SCI during the subacute period can facilitate regeneration of nervous tissue in rats and pigs. These results, for the first time, provide robust support for the use of AD-MSC to treat subacute SCI.

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.

Spinal cord injury (SCI) remains one of the current medical and social problems, as it causes deep disability in patients. The use of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) is one strategy for stimulating the post-traumatic recovery of the structure and function of the spinal cord. Here, we chose an optimal method for obtaining cytochalasin B-induced EVs, including steps with active vortex mixing for 60 s and subsequent filtration to remove nuclei and disorganized inclusions. The therapeutic potential of repeated intrathecal injection of autologous MSC-derived EVs in the subacute period of pig contused SCI was also evaluated for the first time. In this study, we observed the partial restoration of locomotor activity by stimulating the remyelination of axons and timely reperfusion of nervous tissue.

Extracellular vesicles produced by mesenchymal stem cells (MSC-EVs), including exosomes, microvesicles, and apoptotic bodies, are key mediators of intercellular communication and have attracted increasing attention in recent years as potential therapeutic agents for neurological disorders. Predominantly preclinical investigations, including in vitro and animal model studies, demonstrate that MSC-EVs can enhance axonal growth, promote regeneration of nerve fibers and remyelination, and modulate inflammatory processes in injured nervous tissue. These effects have been observed across multiple neurological conditions, including spinal cord injury, traumatic brain injury, ischemic stroke, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, though primarily in experimental settings. Owing to their ability to carry biologically active molecules and to cross the blood–brain barrier, MSC-EVs have shown potential as vehicles for targeted delivery of therapeutic molecules to the central nervous system. However, the overwhelming majority of evidence remains preclinical, and clinical translation is limited by the scarcity of completed, rigorously controlled human trials. To advance toward clinical application, further research is required to standardize methods for vesicle isolation, characterization, and delivery, establish optimal dosing regimens, and develop robust quality control standards. A more comprehensive understanding of MSC-EVs signaling mechanisms may facilitate the future development of therapeutic strategies, contingent upon rigorous validation in well-designed clinical studies.