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

Abstract

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.

Mesenchymal Stem Cell-Derived Exosomes Reduce A1 Astrocytes via Downregulation of Phosphorylated NFκB P65 Subunit in Spinal Cord Injury

“…Our findings suggested that both MSCs and MSC-exo displayed suppressive effects on A1 astrocytes, and showed an equal neuroprotective effect following SCI. Consistent with previous studies showing that MSC application decreased GFAP expression [67,68], we found the MSCs and MSC-exo not only downregulated the general reactivity of astrocytes (GFAP) but also reduced the A1 proportion in the whole astrocytes.…”

Mesenchymal stem cells therapy for spinal cord contusion: a comparative study on small and large animal models

“…Previously we hypothesized, that the application AD-MSCs would increase the number of muscle fibers. However, the morphometry of the calf muscles did not reveal any significant changes in the number of muscle fibers between the control and experimental groups (Mukhamedshina et al, 2018).…”

“…These specific features of MSCs support their potential for treatment of neurodegenerative conditions and traumatic brain and spinal cord injury. Multiple findings suggest that MCSs could promote regeneration of nervous tissues in the brain and spinal cord (Bianco et al, 2016;Mukhamedshina et al, 2018).…”

“…Biopolymer matrices are commonly used to maintain transplanted cells and optimize the microenvironment to increase cell survival and control distribution of bio-active molecules released by the implanted cells (Assunção-Silva et al, 2015; Caron et al, 2016;Zhao et al, 2017). The combined application of MSCs with a matrix could provide a safe and effective approach for cell transplantation in humans with SCI (Caron et al, 2016;Sabino et al, 2018;Mukhamedshina et al, 2018).…”

Application of stem cells and chitosan in the repair of spinal cord injury

“…Stem cell‐based replacement strategy has become a novel way to solve the cytology problem in SCI repair (Mukhamedshina et al, 2018; Xiang and Chen, 2012; Schizas et al, 2018; Nagashima et al, 2017). There are two main mechanisms underlying stem cell‐based transplantation strategy for SCI repair, differentiation into neurons or glial cells for replacing the lost cells (Nagashima et al, 2017; Sugiyama et al, 2019) and secretion of neurotrophic factors for protection of neurons (Kim et al, 2018; Kim et al, 2014).…”