Mukhamedshina, Y. | Search bioRxiv

bioRxiv2024

Local cytokine changes in response to mesenchymal stem cell-derived extracellular vesicles-based therapy in rat spinal cord injury

AimTo investigate the effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), encapsulated in a fibrin matrix (FM), on pro-inflammatory and anti-inflammatory cytokine levels in a rat model of spinal cord injury (SCI) 60 days post-injury. MethodsMSCs were isolated from rat adipose tissue and cultured to obtain MSC-EVs using cytochalasin B. MSC-EVs encapsulated in the FM were applied to the injury site at doses of 5 and 10 {micro}g. Four experimental groups included SCI without treatment, SCI with FM application, and SCI with FM+EVs at 5 and 10 {micro}g doses. A multiplex assay was conducted to measure 23 cytokines in spinal cord tissue homogenates. ResultsFM application to the injury site exhibited both pro- and anti-inflammatory cytokine shifts, with the most pronounced effect for G-CSF (2.8-fold) potentially due to the hemostatic properties of the FM. MSC-EVs led to significant modulation of cytokine levels. In the SCI FM+EVs10 group, concentrations of IL-10, IL-1b, IL-5, and IL-17A were significantly lower compared to the SCI and SCI FM groups. Here the most pronounced change was observed for IL-10, which decreased by 2.4-fold. ConclusionCombined treatment with MSC-EVs and FM significantly influenced pro- and anti-inflammatory cytokine levels, demonstrating a dose-dependent effect. These findings highlight the potential of EVs to modulate inflammatory responses and promote regeneration in the chronic phase of spinal cord injury.

neuroscience↗

bioRxiv2019

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

Here, we provided 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 a small (rat) and large (pig) spinal cord injury (SCI) model during sub-acute period of spinal contusion. Results of behavioral, electrophysiological, histological assessment, as well as results of immunohistochemistry and RT-PCR analysis suggest that application of AD-MSCs combined with a fibrin matrix in a 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 therapy with an autologous application of AD-MSCs was also confirmed in subacute period after spinal contusion in pigs (6 weeks after injury), however, with only partial replication of the findings observed in rats, i.e. (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. The results of this study suggest that 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.

cell biology↗