Oxygen –Glucose Deprived Peripheral Blood Mononuclear Cells Protect Against Ischemic Stroke

AbstractStroke is the leading cause of severe long-term disability. Cell therapy has recently emerged as an approach to facilitate functional recovery in stroke. Although administration of peripheral blood mononuclear cells preconditioned by oxygen –glucose deprivation (OGD-PBMCs) has been shown to be a therapeutic strategy for ischemic stroke, the recovery mechanisms remain largely unknown. We hypothesised that cell–cell communications within PBMCs and between PBMCs and resident cells are necessary for a polarising protective phenotype. H ere, we investigated the therapeutic mechanisms underlying the effects of OGD-PBMCs through the secretome. We compared levels of transcriptomes, cytokines, and exosomal microRNA in human PBMCs by RNA sequences, Luminex assay, flow cytometric analysis, and western blotting under normoxic and OGD cond itions. We also performed microscopic analyses to assess the identification of remodelling factor-positive cells and evaluate angiogenesis, axonal outgrowth, and functional recovery by blinded examination by administration of OGD-PBMCs after ischemic stroke in Sprague–Dawley rats. We found that th e therapeutic potential of OGD-PBMCs was mediated by a polarised protective state through decreased levels of exosomal miR-155-5p, and upregulation of vascular endothelial growth factor and a pluripotent stem cell marker stage-specific embryonic antigen-3 through the hypoxia-inducible factor-1α axi s. After administration of OGD-PBMCs, microenvi...
Source: Neurotherapeutics - Category: Neurology Source Type: research