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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

Schematic diagram indicates the nine areas selected.
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fig1: Schematic diagram indicates the nine areas selected.

Mentions: Positive staining within nine areas (see the schematic diagram at Figures 1 and 4 from the cortex, four from the striatum, and one from the corpus callosum) selected along the IBZ in these groups was digitized under a × 40 objective (BX40; Olympus Optical, Center Valley, PA, USA) using a 3-CCD color video camera (DXC-970MD, Sony, Teaneck, NJ, USA) interfaced with the MCID software.21 For the analysis of neurite remodeling, the area percentage of positive staining signals within the IBZ based on evaluation of an average of three histology slides (8-μm thick, every 10-slide interval) from the standard block of each animal was analyzed using the MCID software. For the quantification of new generated cells and double staining for neurogenesis and angiogenesis, the BrdU-labeled cells in each field and the percentage of double-stained cells were counted and calculated to present indices of neurogenesis and angiogenesis.


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)

Schematic diagram indicates the nine areas selected.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Schematic diagram indicates the nine areas selected.
Mentions: Positive staining within nine areas (see the schematic diagram at Figures 1 and 4 from the cortex, four from the striatum, and one from the corpus callosum) selected along the IBZ in these groups was digitized under a × 40 objective (BX40; Olympus Optical, Center Valley, PA, USA) using a 3-CCD color video camera (DXC-970MD, Sony, Teaneck, NJ, USA) interfaced with the MCID software.21 For the analysis of neurite remodeling, the area percentage of positive staining signals within the IBZ based on evaluation of an average of three histology slides (8-μm thick, every 10-slide interval) from the standard block of each animal was analyzed using the MCID software. For the quantification of new generated cells and double staining for neurogenesis and angiogenesis, the BrdU-labeled cells in each field and the percentage of double-stained cells were counted and calculated to present indices of neurogenesis and angiogenesis.

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