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Neural stem cells traffic functional mitochondria via extracellular vesicles

dc.rights.licenseopenen_US
dc.contributor.authorPERUZZOTTI-JAMETTI, Luca
dc.contributor.authorBERNSTOCK, Joshua D.
dc.contributor.authorWILLIS, Cory M.
dc.contributor.authorMANFERRARI, Giulia
dc.contributor.authorROGALL, Rebecca
dc.contributor.authorFERNANDEZ-VIZARRA, Erika
dc.contributor.authorWILLIAMSON, James C.
dc.contributor.authorBRAGA, Alice
dc.contributor.authorVAN DEN BOSCH, Aletta
dc.contributor.authorLEONARDI, Tommaso
dc.contributor.authorKRZAK, Grzegorz
dc.contributor.authorKITTEL, Agnes
dc.contributor.authorBENINCA, Cristiane
dc.contributor.authorVICARIO, Nunzio
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorTAN, Sisareuth
dc.contributor.authorBASTOS, Carlos
dc.contributor.authorBICCI, Iacopo
dc.contributor.authorIRACI, Nunzio
dc.contributor.authorSMITH, Jayden A.
dc.contributor.authorPEACOCK, Ben
dc.contributor.authorMULLER, Karin H.
dc.contributor.authorLEHNER, Paul J.
dc.contributor.authorBUZAS, Edit Iren
dc.contributor.authorFARIA, Nuno
dc.contributor.authorZEVIANI, Massimo
dc.contributor.authorFREZZA, Christian
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorBRISSON, Alain
dc.contributor.authorMATHESON, Nicholas J.
dc.contributor.authorVISCOMI, Carlo
dc.contributor.authorPLUCHINO, Stefano
dc.date.accessioned2021-07-01T09:47:00Z
dc.date.available2021-07-01T09:47:00Z
dc.date.issued2021
dc.identifier.issn1544-9173en_US
dc.identifier.otherhttp://proteomecentral.proteomexchange.org/en_US
dc.identifier.otherhttps://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001166#sec049en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/94953
dc.description.abstractEnNeural stem cell (NSC) transplantation induces recovery in animal models of central nervous system (CNS) diseases. Although the replacement of lost endogenous cells was originally proposed as the primary healing mechanism of NSC grafts, it is now clear that transplanted NSCs operate via multiple mechanisms, including the horizontal exchange of therapeutic cargoes to host cells via extracellular vesicles (EVs). EVs are membrane particles trafficking nucleic acids, proteins, metabolites and metabolic enzymes, lipids, and entire organelles. However, the function and the contribution of these cargoes to the broad therapeutic effects of NSCs are yet to be fully understood. Mitochondrial dysfunction is an established feature of several inflammatory and degenerative CNS disorders, most of which are potentially treatable with exogenous stem cell therapeutics. Herein, we investigated the hypothesis that NSCs release and traffic functional mitochondria via EVs to restore mitochondrial function in target cells. Untargeted proteomics revealed a significant enrichment of mitochondrial proteins spontaneously released by NSCs in EVs. Morphological and functional analyses confirmed the presence of ultrastructurally intact mitochondria within EVs with conserved membrane potential and respiration. We found that the transfer of these mitochondria from EVs to mtDNA-deficient L929 Rho(0) cells rescued mitochondrial function and increased Rho(0) cell survival. Furthermore, the incorporation of mitochondria from EVs into inflammatory mononuclear phagocytes restored normal mitochondrial dynamics and cellular metabolism and reduced the expression of pro-inflammatory markers in target cells. When transplanted in an animal model of multiple sclerosis, exogenous NSCs actively transferred mitochondria to mononuclear phagocytes and induced a significant amelioration of clinical deficits. Our data provide the first evidence that NSCs deliver functional mitochondria to target cells via EVs, paving the way for the development of novel (a)cellular approaches aimed at restoring mitochondrial dysfunction not only in multiple sclerosis, but also in degenerative neurological diseases.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enMitochondria
dc.subject.enExosomes
dc.subject.enOuter membrane proteins
dc.subject.enVesicles
dc.subject.enPhagocytes
dc.subject.enComputer software
dc.subject.enPolymerase chain reaction
dc.subject.enProteomics
dc.title.enNeural stem cells traffic functional mitochondria via extracellular vesicles
dc.typeArticle de revueen_US
dc.identifier.doi10.1371/journal.pbio.3001166en_US
dc.subject.halChimie/Matériauxen_US
dc.description.sponsorshipEuropeFP7/2007-2013)-ERCen_US
bordeaux.journalPlos Biologyen_US
bordeaux.volume19en_US
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248en_US
bordeaux.issue4en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03275565
hal.version1
hal.date.transferred2021-07-01T09:47:08Z
hal.exporttrue
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