Postischemic Neuroprotection Associated With Anti-Inflammatory Effects by Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles in Aged Mice

Small extracellular vesicles (sEVs) obtained from mesenchymal stromal cells (MSCs) were shown to induce ischemic neuroprotection in mice by modulating the brain infiltration of leukocytes and, specifically polymorphonuclear neutrophils. So far, effects of MSC-sEVs were only studied in young ischemic...

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Published in:Stroke (1970) 2022-01, Vol.53 (1), p.e14-e18
Main Authors: Wang, Chen, Börger, Verena, Mohamud Yusuf, Ayan, Tertel, Tobias, Stambouli, Oumaima, Murke, Florian, Freund, Nico, Kleinschnitz, Christoph, Herz, Josephine, Gunzer, Matthias, Popa-Wagner, Aurel, Doeppner, Thorsten R., Giebel, Bernd, Hermann, Dirk M.
Format: Article
Language:English
Subjects:
Aging - physiology
Animals
Brain - blood supply
Brief Reports
Disease Models, Animal
Extracellular Vesicles - metabolism
Female
Humans
Infarction, Middle Cerebral Artery - therapy
Male
Mesenchymal Stem Cells - cytology
Mice
Mice, Inbred C57BL
Neurons - cytology
Neuroprotection - physiology
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Summary:Small extracellular vesicles (sEVs) obtained from mesenchymal stromal cells (MSCs) were shown to induce ischemic neuroprotection in mice by modulating the brain infiltration of leukocytes and, specifically polymorphonuclear neutrophils. So far, effects of MSC-sEVs were only studied in young ischemic rodents. We herein examined the effects of MSC-sEVs in aged mice. Male and female C57Bl6/j mice (8-10 weeks or 15-24 months) were exposed to transient intraluminal middle cerebral artery occlusion. Vehicle or sEVs (equivalent of 2×10 MSCs) were intravenously administered. Neurological deficits, ischemic injury, blood-brain barrier integrity, brain leukocyte infiltration, and blood leukocyte responses were evaluated over up to 7 days. MSC-sEV delivery reduced neurological deficits, infarct volume, brain edema, and neuronal injury in young and aged mice of both sexes, when delivered immediately postreperfusion or with 6 hours delay. MSC-sEVs decreased leukocyte and specifically polymorphonuclear neutrophil, monocyte, and macrophage infiltrates in ischemic brains of aged mice. In peripheral blood, the number of monocytes and activated T cells was significantly reduced by MSC-sEVs. MSC-sEVs induce postischemic neuroprotection and anti-inflammation in aged mice.
ISSN:0039-2499
1524-4628
DOI:10.1161/STROKEAHA.121.035821