Haupt, Matteo, Zheng, Xuan, Kuang, Yaoyun, Lieschke, Simone, Janssen, Lisa, Bosche, Bert, Jin, Fengyan, Hein, Katharina, Kilic, Ertugrul, Venkataramani, Vivek, Hermann, Dirk M., Bahr, Mathias and Doeppner, Thorsten R. . Lithium modulates miR-1906 levels of mesenchymal stem cell-derived extracellular vesicles contributing to poststroke neuroprotection by toll-like receptor 4 regulation. Stem Cells Transl. Med.. HOBOKEN: WILEY. ISSN 2157-6580

Full text not available from this repository.

Abstract

Lithium 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Haupt, MatteoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zheng, XuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuang, YaoyunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lieschke, SimoneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janssen, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bosche, BertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jin, FengyanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hein, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kilic, ErtugrulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Venkataramani, VivekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hermann, Dirk M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bahr, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doeppner, Thorsten R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-312227
DOI: 10.1002/sctm.20-0086
Journal or Publication Title: Stem Cells Transl. Med.
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 2157-6580
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MOOD STABILIZERS LITHIUM; BRAIN-BARRIER DISRUPTION; FOCAL CEREBRAL-ISCHEMIA; BONE-MARROW; NEUROLOGICAL RECOVERY; INTRACEREBRAL HEMORRHAGE; PROTEASOME INHIBITION; FUNCTIONAL RECOVERY; HYPOXIA-ISCHEMIA; PROGENITOR CELLSMultiple languages
Cell & Tissue EngineeringMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31222

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item