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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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Related in: MedlinePlus

Exosome treatment improves neurologic outcome. Foot-fault test (A) and modified neurologic severity score (B) data show that rats that received exosomes have significant functional enhancement starting 2 weeks after treatment, respectively. *P<0.05, mean±s.d., n=6/group. MCAo, middle cerebral artery occlusion; PBS, phosphate-buffered saline.
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fig2: Exosome treatment improves neurologic outcome. Foot-fault test (A) and modified neurologic severity score (B) data show that rats that received exosomes have significant functional enhancement starting 2 weeks after treatment, respectively. *P<0.05, mean±s.d., n=6/group. MCAo, middle cerebral artery occlusion; PBS, phosphate-buffered saline.

Mentions: The sensorimotor performance of the stroke severity was assessed by measuring foot-fault and mNSS. All rats exhibited severe functional deficit at postoperative day 1, followed by gradual improvement within the 4-week experimental course. Compared with the PBS-treated group, animals that received exosomes exhibited significant functional enhancement in the foot-fault test (Figure 2A) and mNSS (Figure 2B) starting 2 weeks after treatment (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)

Exosome treatment improves neurologic outcome. Foot-fault test (A) and modified neurologic severity score (B) data show that rats that received exosomes have significant functional enhancement starting 2 weeks after treatment, respectively. *P<0.05, mean±s.d., n=6/group. MCAo, middle cerebral artery occlusion; PBS, phosphate-buffered saline.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Exosome treatment improves neurologic outcome. Foot-fault test (A) and modified neurologic severity score (B) data show that rats that received exosomes have significant functional enhancement starting 2 weeks after treatment, respectively. *P<0.05, mean±s.d., n=6/group. MCAo, middle cerebral artery occlusion; PBS, phosphate-buffered saline.
Mentions: The sensorimotor performance of the stroke severity was assessed by measuring foot-fault and mNSS. All rats exhibited severe functional deficit at postoperative day 1, followed by gradual improvement within the 4-week experimental course. Compared with the PBS-treated group, animals that received exosomes exhibited significant functional enhancement in the foot-fault test (Figure 2A) and mNSS (Figure 2B) starting 2 weeks after treatment (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