Small extracellular vesicles derived from umbilical cord mesenchymal stem cells repair blood-spinal cord barrier disruption after spinal cord injury through down-regulation of Endothelin-1 in rats

PeerJ, 2023 · DOI: 10.7717/peerj.16311 · Published: October 31, 2023

Simple Explanation

Spinal cord injury (SCI) can cause irreversible neurological dysfunction by disrupting the blood-spinal cord barrier (BSCB), allowing harmful blood cells to infiltrate the spinal cord. Small extracellular vesicles (sEVs) from umbilical cord mesenchymal stem cells (MSCs) show promise as a therapeutic alternative. This study explored how human umbilical cord MSC-derived sEVs (hUC-MSCs-sEVs) affect BSCB permeability after SCI, demonstrating their ability to inhibit BSCB damage, improve neurological repair, and reduce SCI-induced upregulation of prepro-endothelin-1 (prepro-ET-1) mRNA and endothelin-1 (ET-1) peptide expression. The study indicates that hUC-MSCs-sEVs can help maintain BSCB’s structural integrity and promote functional recovery by suppressing ET-1 expression, offering a potential therapeutic approach for SCI.

Study Duration

21 days

Participants

Adult female Sprague–Dawley rats weighing between 220 and 250 g

Evidence Level

Not specified

Key Findings

1
hUC-MSCs-sEVs mitigate BSCB disruption in rats after SCI, as demonstrated by reduced Evans blue and FITC-dextran fluorescence intensity in the injured spinal cord.
2
hUC-MSCs-sEVs reduce SCI-induced ET-1 expression, as evidenced by decreased prepro-ET-1 mRNA and ET-1 peptide levels following sEVs administration.
3
ET-1 is involved in the effects of hUC-MSCs-sEVs on SCI repair, as ET-1 injection significantly reduced the therapeutic effect of sEVs on motor activity and reversed the protective effect conferred by hUC-MSCs-sEVs on BSCB disruption.

Research Summary

This study investigates the therapeutic potential of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hUC-MSCs-sEVs) in repairing the blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) in rats. The findings indicate that hUC-MSCs-sEVs mitigate BSCB disruption, promote functional recovery, and reduce SCI-induced ET-1 expression. The study also demonstrates that ET-1 is involved in the therapeutic effects of hUC-MSCs-sEVs on SCI repair. The research elucidates the mechanism by which hUC-MSCs-sEVs influence BSCB integrity after SCI, suggesting that hUC-MSCs-sEVs may serve as a promising therapeutic approach for SCI.

Practical Implications

Therapeutic Potential

hUC-MSCs-sEVs offer a promising cell-free therapy for SCI, avoiding risks associated with cell-based treatments.

Mechanism Elucidation

The study sheds light on the role of ET-1 in BSCB disruption and the therapeutic effects of hUC-MSCs-sEVs, guiding future research.

Clinical Translation

The findings support the potential clinical application of hUC-MSCs-sEVs in treating SCI patients by preserving BSCB integrity and promoting functional recovery.

Study Limitations

1
The study did not identify the specific components within sEVs responsible for regulating ET-1 and ameliorating BSCB destruction.
2
The study primarily focused on the effect of sEVs on endothelial cells, without thoroughly examining the roles of other spinal cord cell types, such as microglia and astrocytes.
3
The study did not examine ET-1 receptors ETaR and ETbR or additional signaling pathways that are involved in ET-1 intracellular signaling.

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