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Exosomes derived from Wharton's jelly stem cells switch neural progenitor cell fate to oligodendrogenesis
20 September 2018 (online)
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 are based on released factors such as MSC-derived exosomes.
Thus, the aim of this study was to analyse the potency of exosomes from human Wharton's jelly-derived MSC (WJ-MSC) to initiate oligodendroglial cell fate switch in neural progenitor cells (NPC).
WJ-MSC-derived exosomes were isolated from culture supernatants by serial centrifugations. Exosome microRNA (miRNA) content was assessed by real-time PCR. After 72h of co-culture with WJ-MSC-derived exosomes, NPC were evaluated for the expression of markers involved in oligodendroglial specification by real-time PCR.
miRNA that are involved in oligodendroglial cell fate switch (e.g. miR-338) were present in WJ-MSC-derived exosomes. The transcription of Hairy and enhancer of split (HES1), known to be elevated during gliogenesis, was significantly increased in NPC after incubation with exosomes for 72h. The expression of oligodendrogenic miR-338 – 3 p and miR-338 – 5 p were significantly increased after 72h culture with exosomes, whereas the transcription of the astrocyte marker Glial fibrillary acidic protein (GFAP) and the neuronal marker neurogenic differentiation factor 1 (Neurod1) were significantly reduced.
In conclusion, we have shown that isolated WJ-MSC-derived exosomes contained miRNA playing key roles in oligodendrogenesis. Furthermore, WJ-MSC-derived exosomes favor the priming of NPC towards oligodendrogenesis over astrogliogenesis and neurogenesis, which seem to be partially ascribed to exosome-born miR-338.
Financial support by Gottfried and Julia Bangerter-Rhyner Foundation.