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oai:repisalud.isciii.es:20.500.12105/201472024-11-29T05:06:11Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Phinney, Donald G author Di Giuseppe, Michelangelo author Njah, Joel author Sala, Ernest author Shiva, Sruti author St Croix, Claudette M author Stolz, Donna B author Watkins, Simon C author Di, Y. Peter author Leikauf, George D author Kolls, Jay author Riches, David WH author Deiuliis, Giuseppe author Kaminski, Naftali author Boregowda, Siddaraju V author McKenna, David H author Ortiz, Luis A author 2015-10 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. 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. 10.1038/ncomms9472 2041-1723 Nature Communications http://hdl.handle.net/20.500.13003/10690 26442449 L606304741 2-s2.0-84943795327 http://hdl.handle.net/20.500.12105/20147 364926700001 Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs