Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs
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...
| Autores: | , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/20147 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/20147 |
| Access Level: | acceso abierto |
| Palabra clave: | 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 Oxidative Stress Toll-Like Receptor 9 Blotting, Western Mitochondria Extracellular Vesicles 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 |
| Sumario: | 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. |
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