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dc.contributor.authorKuang, Yaoyun
dc.contributor.authorZheng, Xuan
dc.contributor.authorZhang, Lin
dc.contributor.authorAi, Xiaoyu
dc.contributor.authorVenkataramani, Vivek
dc.contributor.authorKılıç, Ertuğrul
dc.contributor.authorHermann, Dirk M.
dc.contributor.authorMajid, Arshad
dc.contributor.authorBaehr, Mathias
dc.contributor.authorDoeppner, Thorsten R.
dc.date.accessioned2021-02-11T07:31:16Z
dc.date.available2021-02-11T07:31:16Z
dc.date.issued2020en_US
dc.identifier.citationKuang, Y., Zheng, X., Zhang, L., Ai, X., Venkataramani, V., Kılıç, E. ... Doeppner, T. R. (2020). Adipose-derived mesenchymal stem cells reduce autophagy in stroke mice by extracellular vesicle transfer of miR-25. Journal of Extracellular Vesicles, 10(1). https://dx.doi.org/10.1002/jev2.12024en_US
dc.identifier.issn2001-3078
dc.identifier.urihttps://dx.doi.org/10.1002/jev2.12024
dc.identifier.urihttps://hdl.handle.net/20.500.12511/6548
dc.description.abstractGrafted mesenchymal stem cells (MSCs) yield neuroprotection in preclinical stroke models by secreting extracellular vesicles (EVs). The neuroprotective cargo of EVs, however, has not yet been identified. To investigate such cargo and its underlying mechanism, primary neurons were exposed to oxygen-glucose-deprivation (OGD) and cocultured with adipose-derived MSCs (ADMSCs) or ADMSC-secreted EVs. Under such conditions, both ADMSCs and ADMSC-secreted EVs significantly reduced neuronal death. Screening for signalling cascades being involved in the interaction between ADMSCs and neurons revealed a decreased autophagic flux as well as a declined p53-BNIP3 activity in neurons receiving either treatment paradigm. However, the aforementioned effects were reversed when ADMSCs were pretreated with the inhibitor of exosomal secretion GW4869 or when Hrs was knocked down. In light of miR-25-3p being the most highly expressed miRNA in ADMSC-EVs interacting with the p53 pathway, further in vitro work focused on this pathway. Indeed, a miR-25-3p oligonucleotide mimic reduced cell death, whereas the anti-oligonucleotide increased autophagic flux and cell death by modulating p53-BNIP3 signalling in primary neurons exposed to OGD. Likewise, native ADMSC-EVs but not EVs obtained from ADMSCs pretreated with the anti-miR-25-3p oligonucleotide (ADMSC-EVs(anti-miR-25-3p)) confirmed the aforementioned in vitro observations in C57BL/6 mice exposed to cerebral ischemia. The infarct size was reduced, and neurological recovery was increased in mice treated with native ADMSC-EVs when compared to ADMSC-EVs(anti-miR-25-3p). ADMSCs induce neuroprotection by improved autophagic flux through secreted EVs containing miR-25-3p. Hence, our work uncovers a novel key factor in naturally secreted ADMSC-EVs for the regulation of autophagy and induction of neuroprotection in a preclinical stroke model.en_US
dc.description.sponsorshipTürkiye Bilimsel ve Teknolojik Araştırma Kurumu (TÜBİTAK)en_US
dc.language.isoengen_US
dc.publisherTaylor & Francis Ltden_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectCerebral Ischemiaen_US
dc.subjectExtracellular Vesiclesen_US
dc.subjectAdipose-Derived Mscsen_US
dc.subjectNeurological Recoveryen_US
dc.subjectAutophagyen_US
dc.titleAdipose-derived mesenchymal stem cells reduce autophagy in stroke mice by extracellular vesicle transfer of miR-25en_US
dc.typearticleen_US
dc.relation.journalJournal of Extracellular Vesiclesen_US
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)en_US
dc.authorid0000-0001-6494-8923en_US
dc.identifier.volume10en_US
dc.identifier.issue1en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1002/jev2.12024en_US


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