Mesenchymal Stem Cell-Derived Extracellular Vesicles Protect Human Corneal Endothelial Cells from Endoplasmic Reticulum Stress-Mediated Apoptosis.
Apoptosis
/ drug effects
Cell Separation
Culture Media, Serum-Free
Endoplasmic Reticulum Stress
/ drug effects
Endothelial Cells
/ drug effects
Endothelium, Corneal
/ pathology
Extracellular Vesicles
/ drug effects
Gene Expression Regulation
/ drug effects
Humans
Mesenchymal Stem Cells
/ drug effects
MicroRNAs
/ genetics
Phosphorylation
/ drug effects
Tunicamycin
/ pharmacology
corneal dystrophy
corneal endothelium
exosomes
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
06 May 2021
06 May 2021
Historique:
received:
29
03
2021
revised:
29
04
2021
accepted:
05
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
22
6
2021
Statut:
epublish
Résumé
Corneal endothelial dystrophy is a relevant cause of vision loss and corneal transplantation worldwide. In the present study, we analyzed the effect of mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) in an in vitro model of corneal dystrophy, characterized by endoplasmic reticulum stress. The effects of MSC-EVs were compared with those of serum-derived EVs, reported to display a pro-angiogenic activity. MSC-EVs were able to induce a significant down-regulation of the large majority of endoplasmic reticulum stress-related genes in human corneal endothelial cells after exposure to serum deprivation and tunicamycin. In parallel, they upregulated the Akt pathway and limited caspase-3 activation and apoptosis. At variance, the effect of the serum EVs was mainly limited to Akt phosphorylation, with minimal or absent effects on endoplasmic reticulum stress modulation and apoptosis prevention. The effects of MSC-EVs were correlated to the transfer of numerous endoplasmic reticulum (ER)-stress targeting miRNAs to corneal endothelial cells. These data suggest a potential therapeutic effect of MSC-EVs for corneal endothelial endoplasmic reticulum stress, a major player in corneal endothelial dystrophy.
Identifiants
pubmed: 34066474
pii: ijms22094930
doi: 10.3390/ijms22094930
pmc: PMC8125791
pii:
doi:
Substances chimiques
Culture Media, Serum-Free
0
MicroRNAs
0
Tunicamycin
11089-65-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : MIUR (Italian Ministry of Health and Research)
ID : ex60%
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