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Postischemic Neuroprotection Associated With Anti-Inflammatory Effects by Mesenchymal Stromal Cell-Derived Small
Chen Wang1,2, Verena Börger3, Ayan Mohamud Yusuf1,2
1Department of Neurology (C.W., A.M.Y., C.K., D.M.H.), University Hospital Essen, Germany.
Background And Purpose:
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.
Methods:
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 2×106 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.
Results:
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.
Conclusions:
MSC-sEVs induce postischemic neuroprotection and anti-inflammation in aged mice.
Insights
Mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) offer neuroprotection in aged mice following ischemic stroke. MSC-sEVs reduce neurological deficits and brain inflammation by modulating immune cell infiltration.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Immunology
Background:
- Mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) show promise for ischemic neuroprotection.
- Previous studies focused on young rodents; effects in aged animals remain largely unexplored.
Purpose of the Study:
- To investigate the therapeutic potential of MSC-sEVs in aged mice subjected to ischemic stroke.
- To evaluate the impact of MSC-sEVs on neurological deficits, brain injury, and immune responses in aged mice.
Main Methods:
- Aged and young mice underwent transient middle cerebral artery occlusion (tMCAO).
- Mice received intravenous MSC-sEVs or vehicle post-reperfusion.
- Neurological deficits, infarct volume, BBB integrity, and leukocyte infiltration were assessed.
Main Results:
- MSC-sEV treatment significantly reduced neurological deficits, infarct volume, and brain edema in both young and aged mice.
- MSC-sEVs decreased leukocyte infiltration, including neutrophils, monocytes, and macrophages, in the ischemic brains of aged mice.
- Peripheral blood analysis revealed reduced monocyte and activated T cell counts post-MSC-sEV treatment.
Conclusions:
- MSC-sEVs effectively induce neuroprotection and exert anti-inflammatory effects in aged mice following ischemic stroke.
- These findings highlight MSC-sEVs as a potential therapeutic strategy for stroke in aging populations.
