Nanovesicles from adipose-derived mesenchymal stem cells inhibit T lymphocyte trafficking and ameliorate chronic experimental autoimmune encephalomyelitis

Abstract Cell based-therapies represent promising strategies for the treatment of neurological diseases. We have previously shown that adipose stem cells (ASC) ameliorate chronic experimental autoimmune encephalomyelitis (EAE). Recent evidence indicates that most ASC paracrine effects are mediated b...

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Autores principales:	Alessia Farinazzo, Stefano Angiari, Ermanna Turano, Edoardo Bistaffa, Silvia Dusi, Serena Ruggieri, Roberta Bonafede, Raffaella Mariotti, Gabriela Constantin, Bruno Bonetti
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/60be3a2ae4e447ec87734d6e61987829
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spelling	oai:doaj.org-article:60be3a2ae4e447ec87734d6e619878292021-12-02T15:08:57ZNanovesicles from adipose-derived mesenchymal stem cells inhibit T lymphocyte trafficking and ameliorate chronic experimental autoimmune encephalomyelitis10.1038/s41598-018-25676-22045-2322https://doaj.org/article/60be3a2ae4e447ec87734d6e619878292018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25676-2https://doaj.org/toc/2045-2322Abstract Cell based-therapies represent promising strategies for the treatment of neurological diseases. We have previously shown that adipose stem cells (ASC) ameliorate chronic experimental autoimmune encephalomyelitis (EAE). Recent evidence indicates that most ASC paracrine effects are mediated by extracellular vesicles, i.e. micro- and nanovesicles (MVs and NVs). We show that preventive intravenous administration of NVs isolated from ASC (ASC-NVs) before disease onset significantly reduces the severity of EAE and decreases spinal cord inflammation and demyelination, whereas therapeutic treatment with ASC-NVs does not ameliorate established EAE. This treatment marginally inhibits antigen-specific T cell activation, while reducing microglial activation and demyelination in the spinal cord. Importantly, ASC-NVs inhibited integrin-dependent adhesion of encephalitogenic T cells in vitro, with no effect on adhesion molecule expression. In addition, intravital microscopy showed that encephalitogenic T cells treated with ASC NVs display a significantly reduced rolling and firm adhesion in inflamed spinal cord vessels compared to untreated cells. Our results show that ASC-NVs ameliorate EAE pathogenesis mainly by inhibiting T cell extravasation in the inflamed CNS, suggesting that NVs may represent a novel therapeutic approach in neuro-inflammatory diseases, enabling the safe administration of ASC effector factors.Alessia FarinazzoStefano AngiariErmanna TuranoEdoardo BistaffaSilvia DusiSerena RuggieriRoberta BonafedeRaffaella MariottiGabriela ConstantinBruno BonettiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alessia Farinazzo Stefano Angiari Ermanna Turano Edoardo Bistaffa Silvia Dusi Serena Ruggieri Roberta Bonafede Raffaella Mariotti Gabriela Constantin Bruno Bonetti Nanovesicles from adipose-derived mesenchymal stem cells inhibit T lymphocyte trafficking and ameliorate chronic experimental autoimmune encephalomyelitis
description	Abstract Cell based-therapies represent promising strategies for the treatment of neurological diseases. We have previously shown that adipose stem cells (ASC) ameliorate chronic experimental autoimmune encephalomyelitis (EAE). Recent evidence indicates that most ASC paracrine effects are mediated by extracellular vesicles, i.e. micro- and nanovesicles (MVs and NVs). We show that preventive intravenous administration of NVs isolated from ASC (ASC-NVs) before disease onset significantly reduces the severity of EAE and decreases spinal cord inflammation and demyelination, whereas therapeutic treatment with ASC-NVs does not ameliorate established EAE. This treatment marginally inhibits antigen-specific T cell activation, while reducing microglial activation and demyelination in the spinal cord. Importantly, ASC-NVs inhibited integrin-dependent adhesion of encephalitogenic T cells in vitro, with no effect on adhesion molecule expression. In addition, intravital microscopy showed that encephalitogenic T cells treated with ASC NVs display a significantly reduced rolling and firm adhesion in inflamed spinal cord vessels compared to untreated cells. Our results show that ASC-NVs ameliorate EAE pathogenesis mainly by inhibiting T cell extravasation in the inflamed CNS, suggesting that NVs may represent a novel therapeutic approach in neuro-inflammatory diseases, enabling the safe administration of ASC effector factors.
format	article
author	Alessia Farinazzo Stefano Angiari Ermanna Turano Edoardo Bistaffa Silvia Dusi Serena Ruggieri Roberta Bonafede Raffaella Mariotti Gabriela Constantin Bruno Bonetti
author_facet	Alessia Farinazzo Stefano Angiari Ermanna Turano Edoardo Bistaffa Silvia Dusi Serena Ruggieri Roberta Bonafede Raffaella Mariotti Gabriela Constantin Bruno Bonetti
author_sort	Alessia Farinazzo
title	Nanovesicles from adipose-derived mesenchymal stem cells inhibit T lymphocyte trafficking and ameliorate chronic experimental autoimmune encephalomyelitis
title_short	Nanovesicles from adipose-derived mesenchymal stem cells inhibit T lymphocyte trafficking and ameliorate chronic experimental autoimmune encephalomyelitis
title_full	Nanovesicles from adipose-derived mesenchymal stem cells inhibit T lymphocyte trafficking and ameliorate chronic experimental autoimmune encephalomyelitis
title_fullStr	Nanovesicles from adipose-derived mesenchymal stem cells inhibit T lymphocyte trafficking and ameliorate chronic experimental autoimmune encephalomyelitis
title_full_unstemmed	Nanovesicles from adipose-derived mesenchymal stem cells inhibit T lymphocyte trafficking and ameliorate chronic experimental autoimmune encephalomyelitis
title_sort	nanovesicles from adipose-derived mesenchymal stem cells inhibit t lymphocyte trafficking and ameliorate chronic experimental autoimmune encephalomyelitis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/60be3a2ae4e447ec87734d6e61987829
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Nanovesicles from adipose-derived mesenchymal stem cells inhibit T lymphocyte trafficking and ameliorate chronic experimental autoimmune encephalomyelitis

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