Human Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Attenuate Blood-Spinal Cord Barrier Disruption via the TIMP2/MMP Pathway After Acute Spinal Cord Injury.
Animals
Blood-Brain Barrier
/ metabolism
Disease Models, Animal
Exosomes
/ metabolism
Female
Matrix Metalloproteinases
/ metabolism
Mesenchymal Stem Cell Transplantation
/ methods
Mesenchymal Stem Cells
/ metabolism
Rats
Rats, Sprague-Dawley
Spinal Cord Injuries
/ metabolism
Tissue Inhibitor of Metalloproteinase-2
/ metabolism
Blood–spinal cord barrier
Bone marrow mesenchymal stem cells
Exosomes
Spinal cord injury
Tissue inhibitors of matrix metalloproteinases 2
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
received:
23
07
2021
accepted:
13
09
2021
pubmed:
24
9
2021
medline:
18
3
2022
entrez:
23
9
2021
Statut:
ppublish
Résumé
After spinal cord injury (SCI), destruction of the blood-spinal cord barrier (BSCB) results in infiltration of blood cells, such as neutrophils and macrophages, leading to permanent neurological dysfunction. Previous studies have shown that human bone marrow mesenchymal stem cell (BMSC)-derived exosomes have a beneficial neuroprotective effect in SCI models. However, whether BMSC-Exos contribute to the integrity of the BSCB has not been clarified. The purpose of this study was to investigate the mechanism of BMSC-Exo-induced changes in the permeability of the BSCB after SCI. Here, we first used BMSC-Exos to treat an SCI rat model, showing that BMSC-Exos can inhibit BSCB permeability damage and improve spontaneous repair. Next, we found that tissue inhibitors of matrix metalloproteinase 2 (TIMP2) have been shown to play an important role in the function of BMSC-Exos by inhibiting the matrix metalloproteinase (MMP) pathway, thereby reducing the reduction of cell junction proteins. Therefore, we constructed siTIMP2 to knock out TIMP2 in BMSC-Exos, which caused the activity of BMSC-Exos to be significantly weakened. Finally, we constructed an in vitro model of BSCB with HBMECs and verified that TIMP2 in BMSC-Exos in vitro can also alleviate BSCB damage. This proof-of-principle study demonstrates that BMSC-Exos can preserve the integrity of the BSCB and improve functional recovery after SCI through the TIMP2/MMP signaling pathway.
Identifiants
pubmed: 34554399
doi: 10.1007/s12035-021-02565-w
pii: 10.1007/s12035-021-02565-w
doi:
Substances chimiques
Timp2 protein, rat
0
Tissue Inhibitor of Metalloproteinase-2
127497-59-0
Matrix Metalloproteinases
EC 3.4.24.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6490-6504Subventions
Organisme : national natural science foundation of china
ID : NSFC 81272001
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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