Changes of the cytokine profile in blood serum and in the area of traumatic spinal cord injury (SCI) in rats were dealt with in this article. Our study has shown that an inflammatory reaction and immunological response are not limited within the CNS after SCI, but widespread. This fact was confirmed by changes detected in a cytokine profile in blood serum samples (MIP-1α, IL-1α, IL 2, IL-5, IL-1β, MCP-1, RANTES). There were also changes in the levels of MIP-1α, IL-1α, IL-2, IL-5, IL-18, GM-CSF, IL-17α, IFN-γ, IL-10, IL 13, MCP-1, GRO KC CINC-1 in samples of the rat injured spinal cord. The results underscore the complex cytokine network imbalance exhibited by SCI and show significant changes in concentrations of 14 cytokines/chemokines with different inflammatory and immunological activities.

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.

A spinal cord injury (SCI) initiates a number of cascades of biochemical reactions and intercellular interactions, the outcome of which determines the regenerative potential of the nervous tissue and opens up capacities for preserving its functions. The key elements of the above-mentioned processes are microglia. Many assumptions have been put forward, and the first evidence has been obtained, suggesting that, depending on the severity of SCI and the post-traumatic period, microglia behave differently. In this regard, we conducted a study to assess the microglia behavior in the model of mild, moderate and severe SCI in vitro for various post-traumatic periods. We reported for the first time that microglia make a significant contribution to both anti- and pro-inflammatory patterns for a prolonged period after severe SCI (60 dpi), while reduced severities of SCI do not lead to prolonged activation of microglia. The study also revealed the following trend: the greater the severity of the SCI, the lower the proliferative and phagocytic activity of microglia, which is true for all post-traumatic periods of SCI.

Microglial cells are known as important mediators of inflammation and immune response in the central nervous system (CNS). However, a neuroprotective role of these cells in post-traumatic processes should not be overlooked. Microglial cells are the first to respond to CNS injury and are further involved in all critical events of pathogenesis. When activated microglia clear the cellular debris and release anti- and proinflammatory cytokines and chemokines, nitric oxide, neurotrophins, and antioxidants capable of producing both neurotoxic and neuroprotective effects. The aim of this study was to determine to what extent the phagocytic activity of microglia in an acute period of spinal cord injury (SCI) in rats can effect the post-traumatic processes. For this purpose we implanted genetically modified Ad5-EGFP or Ad5-GDNF microglial cells into the area of acute SCI. Our experiments demonstrate that the area of intact tissue was lower in the group transplanted with Ad5-GDNF-transduced microglial cells with reduced phagocytic activity than that in the group of animals transplanted with Ad5-EGFP-transduced microglia cells which did not affect the cell activity. At the same time, there was no significant difference in the functional recovery index between these groups. Thus, the increased number of microglia cells with good phagocytic activity in the area of acute SCI may contribute to the improved nervous tissue integrity without a significant effect on the functional recovery within 30 days after injury.