Oxygen-Glucose Deprived Peripheral Blood Mononuclear Cells Protect Against Ischemic Stroke.
HIF-1α
Oxygen–glucose deprivation
Regeneration
Remodelling factor
SSEA-3
miR-155-5p
Journal
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
ISSN: 1878-7479
Titre abrégé: Neurotherapeutics
Pays: United States
ID NLM: 101290381
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
accepted:
25
05
2023
pmc-release:
01
09
2024
medline:
7
9
2023
pubmed:
19
6
2023
entrez:
19
6
2023
Statut:
ppublish
Résumé
Stroke 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. Here, 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 conditions. 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 the 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 axis. After administration of OGD-PBMCs, microenvironment changes in resident microglia by the secretome promoted angiogenesis and axonal outgrowth, resulting in functional recovery after cerebral ischemia. Our findings revealed the mechanisms underlying the refinement of the neurovascular unit by secretome-mediated cell-cell communications through reduction of miR-155-5p from OGD-PBMCs, highlighting the therapeutic potential carrier of this approach against ischemic stroke.
Identifiants
pubmed: 37335500
doi: 10.1007/s13311-023-01398-w
pii: 10.1007/s13311-023-01398-w
pmc: PMC10480381
doi:
Substances chimiques
Oxygen
S88TT14065
Glucose
IY9XDZ35W2
Vascular Endothelial Growth Factor A
0
MicroRNAs
0
MIRN155 microRNA, rat
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1369-1387Informations de copyright
© 2023. The American Society for Experimental Neurotherapeutics, Inc.
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