Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/20147
Título
Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs
Autor(es)
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 WH | Deiuliis, Giuseppe | Kaminski, Naftali | Boregowda, Siddaraju V | McKenna, David H | Ortiz, Luis A
Fecha de publicación
2015-10
Cita
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.
Idioma
Inglés
Tipo de documento
research article
Resumen
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.
MESH
Oxidative Stress | Toll-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 Señal | Animales | 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
Versión en línea
DOI
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