One Step Closer to Remyelination after Perinatal Brain Damage: Wharton’s Jelly Mesenchymal Stem Cell-Derived Exosomes Drive Neural Progenitors towards Oligodendroglial Cell Fate

Jörger Messerli, Marianne; Spinelli, Marialuigia; Oppliger, Byron; Thomi, Gierin Florence; Haesler, Valérie; Surbek, Daniel; Schoeberlein, Andreina (March 2018). One Step Closer to Remyelination after Perinatal Brain Damage: Wharton’s Jelly Mesenchymal Stem Cell-Derived Exosomes Drive Neural Progenitors towards Oligodendroglial Cell Fate. Reproductive sciences, 25(Suppl 1), 319A-320A. Sage

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INTRODUCTION: The loss of oligodendrocyte progenitor cells leading to overall hypomyelination of the brain is a major hallmark in perinatal brain damage. Experimental transplantations of mesenchymal stem cells (MSC) in animal models of perinatal brain damage strongly indicate that the regenerative effects rely on released factors such as MSC-derived exosomes. METHODS: Thus, the aim of this study is to investigate the capacity of exosomes from human Wharton’s jelly-derived MSC (WJ-MSC) to determine neural progenitor cells (NPC) towards oligodendroglial cell fate. WJ-MSC-derived exosomes were isolated from culture supernatants by serial high-speed and ultracentrifugations. Exosome microRNA (miRNA) content was assessed by real-time PCR. After 72 h of co-culture with WJ-MSC-derived EV, NPC were evaluated for the expression of markers involved in oligodendroglial specification and differentiation by real-time PCR. RESULTS: miRNA that are involved in oligodendroglial cell fate specification and differentiation (miR-338, miR-9, miR-19b, miR-138) were present in WJ-MSC-derived exosomes. The expression of miR-338-3p, known to trigger oligodendrocyte specification, was significantly increased in NPC after co-culture with exosomes. In addition, the gene expression of the transcription factor neurogenic differentiation factor 1 (Neurod1), which blocks oligodendrogenic specification and is repressed by miR-338, was significantly reduced in NPC after co-culture with exosomes. Furthermore, the gene expression of the transcription factor Hairy and enhancer of split (HES1) induced by the Notch signaling pathway, which is activated during oligodendroglial specification, was significantly elevated in NPC after incubation with exosomes. CONCLUSION: In conclusion, isolated WJ-MSC-derived exosomes expressed miRNA having key roles in oligodendrogenesis. Exosomes induced NPC towards oligodendroglial cell fate, ascribing a promising role in neuroregeneration to WJ-MSC-derived exosomes. Financial support by Gottfried and Julia Bangerter-Rhyner Foundation

Item Type:

Conference or Workshop Item (Poster)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pränatale Medizin
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:

Jörger Messerli, Marianne; Spinelli, Marialuigia; Oppliger, Byron; Thomi, Gierin Florence; Surbek, Daniel and Schoeberlein, Andreina

Subjects:

500 Science
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1933-7191

Publisher:

Sage

Funders:

[24] Gottfried und Julia Bangerter- Rhyner Stiftung

Language:

English

Submitter:

Andreina Schoeberlein

Date Deposited:

02 Oct 2019 15:31

Last Modified:

22 Oct 2019 23:12

BORIS DOI:

10.7892/boris.129486

URI:

https://boris.unibe.ch/id/eprint/129486

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