Adipose-Derived Mesenchymal Stem Cell Application Combined With Fibrin Matrix Promotes Structural and Functional Recovery Following Spinal Cord Injury in Rats.

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 PDGFßR 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.

Transplantation of Microglia in the Area of Spinal Cord Injury in an Acute Period Increases Tissue Sparing, but Not Functional Recovery.

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.