Intrathecal Administration of the Extracellular Vesicles Derived From Human Wharton's Jelly Stem Cells Inhibit Inflammation and Attenuate the Activity of Inflammasome Complexes After Spinal Cord Injury in Rats Publisher Pubmed



Noori L¹ ; Arabzadeh S² ; Mohamadi Y³ ; Mojaverrostami S¹ ; Mokhtari T^{4, 5} ; Akbari M¹ ; Hassanzadeh G^{1, 6, 7}
Source: Neuroscience Research Published:2021

Abstract

Activation of inflammasome complexes during spinal cord injury (SCI) lead to conversion of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and interleukin-18 (IL-18) to their active form to initiates the neuroinflammation. Mesenchymal stem cells (MSCs) showed anti-inflammatory properties through their extracellular vehicles (EVs). We investigated immunomodulatory potential of human Wharton's jelly mesenchymal stem cells derived extracellular vesicles (hWJ-MSC-EVs) on inflammasome activity one week after SCI in rats. The gene expression and protein level of IL-1β, IL-18, tumor necrosis factor alpha (TNF-α) and caspase1, were assessed by QPCR and western blotting. Immunohistochemistry (IHC) was done to measure the glial fibrillary acidic protein (GFAP) and Nestin expression. Cell death, histological evaluation and hind limb locomotion was studied by TUNEL assay, Nissl staining and Basso, Beattie, Bresnaham (BBB), respectively. Our finding represented that intrathecally administrated of hWJ-MSC-EVs significantly attenuated expression of the examined factors in both mRNA (P < 0.05 and P ≤ 0.01) and protein levels (P < 0.05 and P ≤ 0.01), decreased GFAP and increased Nestin expression (P < 0.05), reduced cell death and revealed the higher number of typical neurons in ventral horn of spinal cord. Consequently, progress in locomotion. We came to the conclusion that hWJ-MSC-EVs has the potential to control the inflammasome activity after SCI in rats. Moreover, EVs stimulated the neural progenitor cells and modulate the astrocyte activity. © 2020 Elsevier B.V. and Japan Neuroscience Society