Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/20147
Title
Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs
Author(s)
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
Date issued
2015-10
Citation
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.
Language
Inglés
Document type
research article
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.
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
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