Tscherrig, Vera; Cottagnoud, Sophie; Haesler, Valérie; Renz, Patricia; Surbek, Daniel; Schoeberlein, Andreina; Joerger-Messerli, Marianne Simone (2023). MicroRNA Cargo in Wharton's Jelly MSC Small Extracellular Vesicles: Key Functionality to In Vitro Prevention and Treatment of Premature White Matter Injury. Stem cell reviews and reports, 19(7), pp. 2447-2464. Springer 10.1007/s12015-023-10595-1
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Preterm birth is the leading cause of childhood morbidity and mortality and can result in white matter injury (WMI), leading to long-term neurological disabilities with global health burden. Mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEV) are a promising therapeutic agent for treating perinatal neurological injury. They carry microRNAs (miRNAs) predicted to be involved in the onset of premature WMI. We hypothesize that miRNAs have a key function in the beneficial effects of MSC-sEV. We isolated MSC from umbilical cord tissue, the Wharton's jelly (WJ), and purified small extracellular vesicles (sEV) from WJ-MSC culture supernatant by ultracentrifugation and size exclusion chromatography. The miRNA content was quantified by real-time polymerase chain reaction. A luciferase gene assay validated silencing of TP53 and TAOK1, which we previously identified as predicted target genes of MSC-sEV miRNAs by Next Generation Sequencing and pathway enrichment analysis. The impact of sEV miRNAs on oligodendroglial maturation and neuronal apoptosis was evaluated using an in vitro oxygen-glucose deprivation model (OGD/R) by knocking-down DROSHA in WJ-MSC, which initiates miRNA processing. WJ-MSC-sEV contained miRNAs involved in WMI, namely hsa-miR-22-3p, hsa-miR-21-5p, hsa-miR-27b-3p, and the hsa-let-7 family. The luciferase assay strongly indicated an inhibitory effect of sEV miRNAs on the gene expression of TP53 and TAOK1. Small EV initiated oligodendrocyte maturation and reduced OGD/R-mediated neuronal apoptosis. Knocking-down DROSHA in WJ-MSC reduced the expression of sEV miRNAs and led to the loss of their beneficial effects. Our in vitro study strongly indicates the key function of miRNAs in the therapeutic potential of WJ-MSC-sEV in premature WMI.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) 04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Tscherrig, Vera, Cottagnoud, Sophie Manon, Haesler, Valérie, Renz, Patricia Verena, Surbek, Daniel, Schoeberlein, Andreina, Jörger, Marianne |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1550-8943 |
Publisher: |
Springer |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
02 Aug 2023 11:19 |
Last Modified: |
17 Oct 2023 00:13 |
Publisher DOI: |
10.1007/s12015-023-10595-1 |
PubMed ID: |
37523115 |
Uncontrolled Keywords: |
Premature white matter injury Wharton’s jelly mesenchymal stromal cells microRNA small extracellular vesicles |
BORIS DOI: |
10.48350/185166 |
URI: |
https://boris.unibe.ch/id/eprint/185166 |
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