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Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats.

Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M - J. Cereb. Blood Flow Metab. (2013)

Bottom Line: Axonal density and synaptophysin-positive areas were significantly increased along the ischemic boundary zone of the cortex and striatum in MCAo rats treated with exosomes compared with PBS control.Exosome treatment significantly increased the number of newly formed doublecortin (a marker of neuroblasts) and von Willebrand factor (a marker of endothelial cells) cells.Our results suggest that intravenous administration of cell-free MSC-generated exosomes post stroke improves functional recovery and enhances neurite remodeling, neurogenesis, and angiogenesis and represents a novel treatment for stroke.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Henry Ford Health Sciences Center, Henry Ford Hospital, Detroit, Michigan, USA.

ABSTRACT
Here, for the first time, we test a novel hypothesis that systemic treatment of stroke with exosomes derived from multipotent mesenchymal stromal cells (MSCs) promote neurovascular remodeling and functional recovery after stroke in rats. Adult male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAo) followed by tail vein injection of 100 μg protein from MSC exosome precipitates or an equal volume of vehicle phosphate-buffered saline (PBS) (n=6/group) 24 hours later. Animals were killed at 28 days after stroke and histopathology and immunohistochemistry were employed to identify neurite remodeling, neurogenesis, and angiogenesis. Systemic administration of MSC-generated exosomes significantly improved functional recovery in stroke rats compared with PBS-treated controls. Axonal density and synaptophysin-positive areas were significantly increased along the ischemic boundary zone of the cortex and striatum in MCAo rats treated with exosomes compared with PBS control. Exosome treatment significantly increased the number of newly formed doublecortin (a marker of neuroblasts) and von Willebrand factor (a marker of endothelial cells) cells. Our results suggest that intravenous administration of cell-free MSC-generated exosomes post stroke improves functional recovery and enhances neurite remodeling, neurogenesis, and angiogenesis and represents a novel treatment for stroke.

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Exosomes increase neurite remodeling in the ischemic boundary zone (IBZ). Bielschowsky silver and Luxol fast blue double staining (A row), SMI-31 immunostaining (B row), and synaptophysin immunostaining (C row) show that exosome treatment increased neurite remodeling and synaptic plasticity in the IBZ of ischemic rats compared with phosphate-buffered saline (PBS) treatment. *P<0.05, respectively. Mean±s.d., n=6/group. Scale bar, 50 μm.
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fig3: Exosomes increase neurite remodeling in the ischemic boundary zone (IBZ). Bielschowsky silver and Luxol fast blue double staining (A row), SMI-31 immunostaining (B row), and synaptophysin immunostaining (C row) show that exosome treatment increased neurite remodeling and synaptic plasticity in the IBZ of ischemic rats compared with phosphate-buffered saline (PBS) treatment. *P<0.05, respectively. Mean±s.d., n=6/group. Scale bar, 50 μm.

Mentions: Double staining for Bielschowsky silver and Luxol fast blue was used to identify axons and myelin in the white matter in the brain, respectively. The white matter in the core lesion area was destroyed and axon–myelin bundles in the IBZ were partially damaged and disorganized after stroke. Axonal density along the IBZ was significantly increased by exosome treatment compared with PBS control at 28 days after MCAo (Figure 3, row A, P<0.05).


Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats.

Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M - J. Cereb. Blood Flow Metab. (2013)

Exosomes increase neurite remodeling in the ischemic boundary zone (IBZ). Bielschowsky silver and Luxol fast blue double staining (A row), SMI-31 immunostaining (B row), and synaptophysin immunostaining (C row) show that exosome treatment increased neurite remodeling and synaptic plasticity in the IBZ of ischemic rats compared with phosphate-buffered saline (PBS) treatment. *P<0.05, respectively. Mean±s.d., n=6/group. Scale bar, 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824189&req=5

fig3: Exosomes increase neurite remodeling in the ischemic boundary zone (IBZ). Bielschowsky silver and Luxol fast blue double staining (A row), SMI-31 immunostaining (B row), and synaptophysin immunostaining (C row) show that exosome treatment increased neurite remodeling and synaptic plasticity in the IBZ of ischemic rats compared with phosphate-buffered saline (PBS) treatment. *P<0.05, respectively. Mean±s.d., n=6/group. Scale bar, 50 μm.
Mentions: Double staining for Bielschowsky silver and Luxol fast blue was used to identify axons and myelin in the white matter in the brain, respectively. The white matter in the core lesion area was destroyed and axon–myelin bundles in the IBZ were partially damaged and disorganized after stroke. Axonal density along the IBZ was significantly increased by exosome treatment compared with PBS control at 28 days after MCAo (Figure 3, row A, P<0.05).

Bottom Line: Axonal density and synaptophysin-positive areas were significantly increased along the ischemic boundary zone of the cortex and striatum in MCAo rats treated with exosomes compared with PBS control.Exosome treatment significantly increased the number of newly formed doublecortin (a marker of neuroblasts) and von Willebrand factor (a marker of endothelial cells) cells.Our results suggest that intravenous administration of cell-free MSC-generated exosomes post stroke improves functional recovery and enhances neurite remodeling, neurogenesis, and angiogenesis and represents a novel treatment for stroke.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Henry Ford Health Sciences Center, Henry Ford Hospital, Detroit, Michigan, USA.

ABSTRACT
Here, for the first time, we test a novel hypothesis that systemic treatment of stroke with exosomes derived from multipotent mesenchymal stromal cells (MSCs) promote neurovascular remodeling and functional recovery after stroke in rats. Adult male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAo) followed by tail vein injection of 100 μg protein from MSC exosome precipitates or an equal volume of vehicle phosphate-buffered saline (PBS) (n=6/group) 24 hours later. Animals were killed at 28 days after stroke and histopathology and immunohistochemistry were employed to identify neurite remodeling, neurogenesis, and angiogenesis. Systemic administration of MSC-generated exosomes significantly improved functional recovery in stroke rats compared with PBS-treated controls. Axonal density and synaptophysin-positive areas were significantly increased along the ischemic boundary zone of the cortex and striatum in MCAo rats treated with exosomes compared with PBS control. Exosome treatment significantly increased the number of newly formed doublecortin (a marker of neuroblasts) and von Willebrand factor (a marker of endothelial cells) cells. Our results suggest that intravenous administration of cell-free MSC-generated exosomes post stroke improves functional recovery and enhances neurite remodeling, neurogenesis, and angiogenesis and represents a novel treatment for stroke.

Show MeSH
Related in: MedlinePlus