Extracellular vesicles derived from DFO-preconditioned canine AT-MSCs reprogram macrophages into M2 phase.

<h4>Background</h4>Mesenchymal stem/stromal cells (MSCs) are effective therapeutic agents that ameliorate inflammation through paracrine effect; in this regard, extracellular vesicles (EVs) have been frequently studied. To improve the secretion of anti-inflammatory factors from MSCs, pre...

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Autores principales:	Su-Min Park, Ju-Hyun An, Jeong-Hwa Lee, Kyung-Bo Kim, Hyung-Kyu Chae, Ye-In Oh, Woo-Jin Song, Hwa-Young Youn
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ba16e6916c22464baabee84acfd19be9
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spelling	oai:doaj.org-article:ba16e6916c22464baabee84acfd19be92021-12-02T20:04:50ZExtracellular vesicles derived from DFO-preconditioned canine AT-MSCs reprogram macrophages into M2 phase.1932-620310.1371/journal.pone.0254657https://doaj.org/article/ba16e6916c22464baabee84acfd19be92021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254657https://doaj.org/toc/1932-6203<h4>Background</h4>Mesenchymal stem/stromal cells (MSCs) are effective therapeutic agents that ameliorate inflammation through paracrine effect; in this regard, extracellular vesicles (EVs) have been frequently studied. To improve the secretion of anti-inflammatory factors from MSCs, preconditioning with hypoxia or hypoxia-mimetic agents has been attempted and the molecular changes in preconditioned MSC-derived EVs explored. In this study, we aimed to investigate the increase of hypoxia-inducible factor 1-alpha (HIF-1α)/cyclooxygenase-2 (COX-2) in deferoxamine (DFO)-preconditioned canine MSC (MSCDFO) and whether these molecular changes were reflected on EVs. Furthermore, we focused on MSCDFO derived EVs (EVDFO) could affect macrophage polarization via the transfer function of EVs.<h4>Results</h4>In MSCDFO, accumulation of HIF-1α were increased and production of COX-2 were activated. Also, Inside of EVDFO were enriched with COX-2 protein. To evaluate the transferring effect of EVs to macrophage, the canine macrophage cell line, DH82, was treated with EVs after lipopolysaccharide (LPS) stimulation. Polarization changes of DH82 were evaluated with quantitative real-time PCR and immunofluorescence analyses. When LPS-induced DH82 was treated with EVDFO, phosphorylation of signal transducer and transcription3 (p-STAT3), which is one of key factor of inducing M2 phase, expression was increased in DH82. Furthermore, treated with EVDFO in LPS-induced DH82, the expression of M1 markers were reduced, otherwise, M2 surface markers were enhanced. Comparing with EVDFO and EVnon.<h4>Conclusion</h4>DFO preconditioning in MSCs activated the HIF-1α/COX-2 signaling pathway; Transferring COX-2 through EVDFO could effectively reprogram macrophage into M2 phase by promoting the phosphorylation of STAT3.Su-Min ParkJu-Hyun AnJeong-Hwa LeeKyung-Bo KimHyung-Kyu ChaeYe-In OhWoo-Jin SongHwa-Young YounPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254657 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Su-Min Park Ju-Hyun An Jeong-Hwa Lee Kyung-Bo Kim Hyung-Kyu Chae Ye-In Oh Woo-Jin Song Hwa-Young Youn Extracellular vesicles derived from DFO-preconditioned canine AT-MSCs reprogram macrophages into M2 phase.
description	<h4>Background</h4>Mesenchymal stem/stromal cells (MSCs) are effective therapeutic agents that ameliorate inflammation through paracrine effect; in this regard, extracellular vesicles (EVs) have been frequently studied. To improve the secretion of anti-inflammatory factors from MSCs, preconditioning with hypoxia or hypoxia-mimetic agents has been attempted and the molecular changes in preconditioned MSC-derived EVs explored. In this study, we aimed to investigate the increase of hypoxia-inducible factor 1-alpha (HIF-1α)/cyclooxygenase-2 (COX-2) in deferoxamine (DFO)-preconditioned canine MSC (MSCDFO) and whether these molecular changes were reflected on EVs. Furthermore, we focused on MSCDFO derived EVs (EVDFO) could affect macrophage polarization via the transfer function of EVs.<h4>Results</h4>In MSCDFO, accumulation of HIF-1α were increased and production of COX-2 were activated. Also, Inside of EVDFO were enriched with COX-2 protein. To evaluate the transferring effect of EVs to macrophage, the canine macrophage cell line, DH82, was treated with EVs after lipopolysaccharide (LPS) stimulation. Polarization changes of DH82 were evaluated with quantitative real-time PCR and immunofluorescence analyses. When LPS-induced DH82 was treated with EVDFO, phosphorylation of signal transducer and transcription3 (p-STAT3), which is one of key factor of inducing M2 phase, expression was increased in DH82. Furthermore, treated with EVDFO in LPS-induced DH82, the expression of M1 markers were reduced, otherwise, M2 surface markers were enhanced. Comparing with EVDFO and EVnon.<h4>Conclusion</h4>DFO preconditioning in MSCs activated the HIF-1α/COX-2 signaling pathway; Transferring COX-2 through EVDFO could effectively reprogram macrophage into M2 phase by promoting the phosphorylation of STAT3.
format	article
author	Su-Min Park Ju-Hyun An Jeong-Hwa Lee Kyung-Bo Kim Hyung-Kyu Chae Ye-In Oh Woo-Jin Song Hwa-Young Youn
author_facet	Su-Min Park Ju-Hyun An Jeong-Hwa Lee Kyung-Bo Kim Hyung-Kyu Chae Ye-In Oh Woo-Jin Song Hwa-Young Youn
author_sort	Su-Min Park
title	Extracellular vesicles derived from DFO-preconditioned canine AT-MSCs reprogram macrophages into M2 phase.
title_short	Extracellular vesicles derived from DFO-preconditioned canine AT-MSCs reprogram macrophages into M2 phase.
title_full	Extracellular vesicles derived from DFO-preconditioned canine AT-MSCs reprogram macrophages into M2 phase.
title_fullStr	Extracellular vesicles derived from DFO-preconditioned canine AT-MSCs reprogram macrophages into M2 phase.
title_full_unstemmed	Extracellular vesicles derived from DFO-preconditioned canine AT-MSCs reprogram macrophages into M2 phase.
title_sort	extracellular vesicles derived from dfo-preconditioned canine at-mscs reprogram macrophages into m2 phase.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/ba16e6916c22464baabee84acfd19be9
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Extracellular vesicles derived from DFO-preconditioned canine AT-MSCs reprogram macrophages into M2 phase.

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