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dc.contributor.authorHaupt, Matteo
dc.contributor.authorZheng, Xuan
dc.contributor.authorKuang, Yaoyun
dc.contributor.authorLieschke, Simone
dc.contributor.authorJanssen, Lisa
dc.contributor.authorBosche, Bert
dc.contributor.authorJin, Fengyan
dc.contributor.authorHein, Katharina
dc.contributor.authorKılıç, Ertuğrul
dc.contributor.authorVenkataramani, Vivek
dc.contributor.authorHermann, Dirk M.
dc.contributor.authorBahr, Mathias
dc.contributor.authorDoeppner, Thorsten R.
dc.identifier.citationHaupt, M., Zheng, X., Kuang, Y., Lieschke, S., Janssen, L., Bosche, B. ... Doeppner, T. R. (2021). Lithium modulates miR-1906 levels of mesenchymal stem cell-derived extracellular vesicles contributing to poststroke neuroprotection by toll-like receptor 4 regulation. Stem Cells Translational Medicine, 10(3), 357-373.
dc.description.abstractLithium is neuroprotective in preclinical stroke models. In addition to that, poststroke neuroregeneration is stimulated upon transplantation of mesenchymal stem cells (MSCs). Preconditioning of MSCs with lithium further enhances the neuroregenerative potential of MSCs, which act by secreting extracellular vesicles (EVs). The present work analyzed, whether MSC preconditioning with lithium modifies EV secretion patterns, enhancing the therapeutic potential of such derived EVs (Li-EVs) in comparison with EVs enriched from native MSCs. Indeed, Li-EVs significantly enhanced the resistance of cultured astrocytes, microglia, and neurons against hypoxic injury when compared with controls and to native EV-treated cells. Using a stroke mouse model, intravenous delivery of Li-EVs increased neurological recovery and neuroregeneration for as long as 3 months in comparison with controls and EV-treated mice, albeit the latter also showed significantly better behavioral test performance compared with controls. Preconditioning of MSCs with lithium also changed the secretion patterns for such EVs, modifying the contents of various miRNAs within these vesicles. As such, Li-EVs displayed significantly increased levels of miR-1906, which has been shown to be a new regulator of toll-like receptor 4 (TLR4) signaling. Li-EVs reduced posthypoxic and postischemic TLR4 abundance, resulting in an inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) signaling pathway, decreased proteasomal activity, and declined both inducible NO synthase and cyclooxygenase-2 expression, all of which culminating in reduced levels of poststroke cerebral inflammation. Conclusively, the present study for the first time demonstrates an enhanced therapeutic potential of Li-EVs compared with native EVs, interfering with a novel signaling pathway that yields both acute neuroprotection an enhanced neurological recovery.en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.subjectCerebral Ischemiaen_US
dc.subjectExtracellular Vesiclesen_US
dc.subjectMesenchymal Stem Cellsen_US
dc.titleLithium modulates miR-1906 levels of mesenchymal stem cell-derived extracellular vesicles contributing to poststroke neuroprotection by toll-like receptor 4 regulationen_US
dc.relation.journalStem Cells Translational Medicineen_US
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US

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