Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Nov;33(11):1711-5.
doi: 10.1038/jcbfm.2013.152. Epub 2013 Aug 21.

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

Hongqi Xin  1 , Yi Li, Yisheng Cui, James J Yang, Zheng Gang Zhang, Michael Chopp
Affiliations

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

Hongqi Xin et al. J Cereb Blood Flow Metab. 2013 Nov.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic diagram indicates the nine areas selected.
Figure 2
Figure 2
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.
Figure 3
Figure 3
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.
Figure 4
Figure 4
Exosomes increase neurogenesis and angiogenesis in the ischemic boundary zone (IBZ). Compared with phosphate-buffered saline (PBS) treatment, the 5-bromodeoxyuridine (BrdU)-labeled cells in the IBZ were significantly increased after exosome treatment (A row). Representative micrographs show the double-stained cells with doublecortin (DCX) and BrdU (B row) or von Willebrand factor (vWF) and BrdU (C row). Compared with PBS treatment, exosome treatment significantly increased the percentage of BrdU–DCX stained cells (B) and BrdU–endothelial cells stained cells in the IBZ (C) in rats after stroke, respectively. *P<0.05, mean±s.d., n=6/group. Scale bar, 50 μm. DAPI, 4′,6-diamidino-2-phenylindole.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Stoorvogel W, Kleijmeer MJ, Geuze HJ, Raposo G. The biogenesis and functions of exosomes. Traffic. 2002;3:321–330. - PubMed
    1. Record M, Subra C, Silvente-Poirot S, Poirot M. Exosomes as intercellular signalosomes and pharmacological effectors. Biochem Pharmacol. 2011;81:1171–1182. - PubMed
    1. Zomer A, Vendrig T, Hopmans ES, van Eijndhoven M, Middeldorp JM, Pegtel DM. Exosomes: fit to deliver small rna. Commun Integr Biol. 2010;3:447–450. - PMC - PubMed
    1. Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteomics. 2010;73:1907–1920. - PubMed
    1. Li T, Yan Y, Wang B, Qian H, Zhang X, Shen L, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev. 2013;22:845–854. - PMC - PubMed

Publication types