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弗元生物-专业的干细胞培养基 >> 资 料 >>产品引用 >>2023年 >> Xue C, 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 r
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Xue C, 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 r

Xue C, Ma X, Guan X, Feng H, Zheng M, Yang X. 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 Oct 31;11:e16311. doi: 10.7717/peerj.16311. PMID: 37927780; PMCID: PMC10624166.

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

Chenhui Xue 1Xun Ma 1 2Xiaoming Guan 1 2Haoyu Feng 1 2Mingkui Zheng 1Xihua Yang 3

Affiliations

  • 1Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, Shanxi, China.

  • 2Department of Orthopedics, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

  • 3Laboratory Animal Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China.


Abstract

Spinal cord injury could cause irreversible neurological dysfunction by destroying the blood-spinal cord barrier (BSCB) and allowing blood cells like neutrophils and macrophages to infiltrate the spinal cord. Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) found in the human umbilical cord have emerged as a potential therapeutic alternative to cell-based treatments. This study aimed to investigate the mechanism underlying the alterations in the BSCB permeability by human umbilical cord MSC-derived sEVs (hUC-MSCs-sEVs) after SCI. First, we used hUC-MSCs-sEVs to treat SCI rat models, demonstrating their ability to inhibit BSCB permeability damage, improve neurological repair, and reduce SCI-induced upregulation of prepro-endothelin-1 (prepro-ET-1) mRNA and endothelin-1 (ET-1) peptide expression. Subsequently, we confirmed that hUC-MSCs-sEVs could alleviate cell junction destruction and downregulate MMP-2 and MMP-9 expression after SCI, contributing to BSCB repair through ET-1 inhibition. Finally, we established an in vitro model of BSCB using human brain microvascular endothelial cells and verified that hUC-MSCs-sEVs could increase the expression of junction proteins in endothelial cells after oxygen-glucose deprivation by ET-1 downregulation. This study indicates that hUC-MSCs-sEVs could help maintain BSCB's structural integrity and promote functional recovery by suppressing ET-1 expression.

Keywords: Blood-spinal cord barrier; Endothelin-1; Exosomes; Spinal cord injury; Stem cells.


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