Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/10690
Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs
Identifiers
DOI: 10.1038/ncomms9472
ISSN: 2041-1723
WOS ID: 000364926700001
Scopus EID: 2-s2.0-84943795327
PMID: 26442449
Embase PUI: L606304741
Share
Statistics
Item usage statisticsMetadata
Show Dublin Core item recordAuthor
Phinney, Donald G.; Di Giuseppe, Michelangelo; Njah, Joel; Sala, Ernest; Shiva, Sruti; St Croix, Claudette M.; Stolz, Donna B.; Watkins, Simon C.; Di, Y. Peter; Leikauf, George D.; Kolls, Jay; Riches, David W. H.; Deiuliis, Giuseppe; Kaminski, Naftali; Boregowda, Siddaraju V.; McKenna, David H.; Ortiz, Luis A.Publication date
2015-10Document type
research articleCitation
Phinney DG, Di Giuseppe M, Njah J, Sala-Llinas E, Shiva S, St Croix CM, et al. Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat Commun. 2015 Oct;6:8472.Abstract
Mesenchymal stem cells (MSCs) and macrophages are fundamental components of the stem cell niche and function coordinately to regulate haematopoietic stem cell self-renewal and mobilization. Recent studies indicate that mitophagy and healthy mitochondrial function are critical to the survival of stem cells, but how these processes are regulated in MSCs is unknown. Here we show that MSCs manage intracellular oxidative stress by targeting depolarized mitochondria to the plasma membrane via arrestin domain-containing protein 1-mediated microvesicles. The vesicles are then engulfed and re-utilized via a process involving fusion by macrophages, resulting in enhanced bioenergetics. Furthermore, we show that MSCs simultaneously shed micro RNA-containing exosomes that inhibit macrophage activation by suppressing Toll-like receptor signalling, thereby de-sensitizing macrophages to the ingested mitochondria. Collectively, these studies mechanistically link mitophagy and MSC survival with macrophage function, thereby providing a physiologically relevant context for the innate immunomodulatory activity of MSCs.
Publisher version
https://dx.doi.org/10.1038/ncomms9472MeSH
Oxidative StressToll-Like Receptor 9
Blotting, Western
Mitochondria
Extracellular Vesicles
Silicosis
Flow Cytometry
Humans
Arrestins
Microscopy, Electron
Toll-Like Receptors
Exosomes
Macrophages
MicroRNAs
Myeloid Differentiation Factor 88
Toll-Like Receptor 4
Cell-Derived Microparticles
Animals
Signal Transduction
Receptors, Immunologic
Mice
DeCS
Transducción de SeñalAnimales
Macrófagos
Citometría de Flujo
Silicosis
Receptor Toll-Like 4
Humanos
Receptores Toll-Like
Arrestinas
Microscopía Electrónica
Vesículas Extracelulares
Receptor Toll-Like 9
Estrés Oxidativo
Receptores Inmunológicos
Micropartículas Derivadas de Células
Ratones
Exosomas
Factor 88 de Diferenciación Mieloide
Mitocondrias
Western Blotting
MicroARNs
This item appears in following Docusalut collections
Hospital Universitario Son Espases - HUSE > Comunicación científicaInstituto de Investigación Sanitaria Islas Baleares - IDISBA > Comunicación científica