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  4. Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier

Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier

Frontiers in Neuroscience, 2019 · DOI: 10.3389/fnins.2019.00209 · Published: March 12, 2019

Spinal Cord InjuryNeurologyGenetics

Simple Explanation

Mesenchymal stem cell (MSC) transplantation has been shown to represent a potential treatment for traumatic spinal cord injury (SCI). Recent studies have suggested that MSC treatment is beneficial owing to paracrine-secreted factors. Extracellular vesicles are considered to be some of the most valuable paracrine molecules. This study demonstrated that administration of bone mesenchymal stem cell-derived extracellular vesicles (BMSC-EV) reduced brain cell death, enhanced neuronal survival and regeneration, and improved motor function compared with the administration of BMSC-EV free culture media (EV-free CM). In summary, this study identified that extracellular vesicles treatment suppressed the migration of pericytes and further improved the integrity of the BSCB via NF-κB p65 signaling in pericytes. The data suggest that extracellular vesicles may serve as a promising treatment strategy for SCI.

Study Duration
28 days
Participants
100 Adult male Sprague–Dawley (SD) rats (200–250 g)
Evidence Level
Not specified

Key Findings

  • 1
    Administration of bone mesenchymal stem cell-derived extracellular vesicles (BMSC-EV) reduced brain cell death, enhanced neuronal survival and regeneration, and improved motor function.
  • 2
    BMSC-EV administration increased BSCB pericyte coverage and decreases BSCB permeability.
  • 3
    BMSC-EV inhibit pericyte migration via the NF-κB p65 pathway.

Research Summary

This study demonstrates that BMSC-EV administration critically improves neuronal regeneration and attenuates nerve cell death, which is beneficial for motor function recovery after SCI. Pericyte migration could be prohibited by BMSC-EV administration via suppression of the activation of the NF-kB signaling pathway, leading to an improvement in the integrity of the BSCB. The study provides the first evidence that BMSC-EV can effectively inhibit the migration of pericytes, thereby maintaining the integrity of the BSCB after SCI.

Practical Implications

Therapeutic potential

Extracellular vesicles may serve as a promising treatment strategy for spinal cord injury.

BSCB Integrity

BMSC-EV improves the structural integrity of the BSCB by inhibiting the migration of pericytes and improving the rate of pericyte coverage.

Neuronal Protection

BMSC-EV administration contributes to neuronal survival, with less apoptosis and promotion of functional recovery observed.

Study Limitations

  • 1
    The extracellular vesicles components involved in the regulation of pericyte migration remain to be elucidated.
  • 2
    We only detected the migration of pericytes 6 h after OGD exposure, making it impossible to identify the exact effect of BMSC-EV.
  • 3
    Observations at longer timepoints should be performed in future experiments.

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