Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis

Abstract Mesenchymal stromal cells (MSCs) are used for ameliorating liver fibrosis and aiding liver regeneration after cirrhosis; Here, we analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs). γ-sEVs effectively ind...

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Autores principales:	Suguru Takeuchi, Atsunori Tsuchiya, Takahiro Iwasawa, Shunsuke Nojiri, Takayuki Watanabe, Masahiro Ogawa, Tomoaki Yoshida, Katsunori Fujiki, Yuta Koui, Taketomo Kido, Yusuke Yoshioka, Mayu Fujita, Junichi Kikuta, Tohru Itoh, Masaaki Takamura, Katsuhiko Shirahige, Masaru Ishii, Takahiro Ochiya, Atsushi Miyajima, Shuji Terai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/ade7176a775045be931db93405b53155
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spelling	oai:doaj.org-article:ade7176a775045be931db93405b531552021-12-02T13:27:07ZSmall extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis10.1038/s41536-021-00132-42057-3995https://doaj.org/article/ade7176a775045be931db93405b531552021-03-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00132-4https://doaj.org/toc/2057-3995Abstract Mesenchymal stromal cells (MSCs) are used for ameliorating liver fibrosis and aiding liver regeneration after cirrhosis; Here, we analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs). γ-sEVs effectively induced anti-inflammatory macrophages with high motility and phagocytic abilities in vitro, while not preventing hepatic stellate cell (HSC; the major source of collagen fiber) activation in vitro. The proteome analysis of MSC-derived sEVs revealed anti-inflammatory macrophage inducible proteins (e.g., annexin-A1, lactotransferrin, and aminopeptidase N) upon IFN-γ stimulation. Furthermore, by enabling CX3CR1+ macrophage accumulation in the damaged area, γ-sEVs ameliorated inflammation and fibrosis in the cirrhosis mouse model more effectively than sEVs. Single cell RNA-Seq analysis revealed diverse effects, such as induction of anti-inflammatory macrophages and regulatory T cells, in the cirrhotic liver after γ-sEV administration. Overall, IFN-γ pre-conditioning altered sEVs resulted in efficient tissue repair indicating a new therapeutic strategy.Suguru TakeuchiAtsunori TsuchiyaTakahiro IwasawaShunsuke NojiriTakayuki WatanabeMasahiro OgawaTomoaki YoshidaKatsunori FujikiYuta KouiTaketomo KidoYusuke YoshiokaMayu FujitaJunichi KikutaTohru ItohMasaaki TakamuraKatsuhiko ShirahigeMasaru IshiiTakahiro OchiyaAtsushi MiyajimaShuji TeraiNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Suguru Takeuchi Atsunori Tsuchiya Takahiro Iwasawa Shunsuke Nojiri Takayuki Watanabe Masahiro Ogawa Tomoaki Yoshida Katsunori Fujiki Yuta Koui Taketomo Kido Yusuke Yoshioka Mayu Fujita Junichi Kikuta Tohru Itoh Masaaki Takamura Katsuhiko Shirahige Masaru Ishii Takahiro Ochiya Atsushi Miyajima Shuji Terai Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis
description	Abstract Mesenchymal stromal cells (MSCs) are used for ameliorating liver fibrosis and aiding liver regeneration after cirrhosis; Here, we analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs). γ-sEVs effectively induced anti-inflammatory macrophages with high motility and phagocytic abilities in vitro, while not preventing hepatic stellate cell (HSC; the major source of collagen fiber) activation in vitro. The proteome analysis of MSC-derived sEVs revealed anti-inflammatory macrophage inducible proteins (e.g., annexin-A1, lactotransferrin, and aminopeptidase N) upon IFN-γ stimulation. Furthermore, by enabling CX3CR1+ macrophage accumulation in the damaged area, γ-sEVs ameliorated inflammation and fibrosis in the cirrhosis mouse model more effectively than sEVs. Single cell RNA-Seq analysis revealed diverse effects, such as induction of anti-inflammatory macrophages and regulatory T cells, in the cirrhotic liver after γ-sEV administration. Overall, IFN-γ pre-conditioning altered sEVs resulted in efficient tissue repair indicating a new therapeutic strategy.
format	article
author	Suguru Takeuchi Atsunori Tsuchiya Takahiro Iwasawa Shunsuke Nojiri Takayuki Watanabe Masahiro Ogawa Tomoaki Yoshida Katsunori Fujiki Yuta Koui Taketomo Kido Yusuke Yoshioka Mayu Fujita Junichi Kikuta Tohru Itoh Masaaki Takamura Katsuhiko Shirahige Masaru Ishii Takahiro Ochiya Atsushi Miyajima Shuji Terai
author_facet	Suguru Takeuchi Atsunori Tsuchiya Takahiro Iwasawa Shunsuke Nojiri Takayuki Watanabe Masahiro Ogawa Tomoaki Yoshida Katsunori Fujiki Yuta Koui Taketomo Kido Yusuke Yoshioka Mayu Fujita Junichi Kikuta Tohru Itoh Masaaki Takamura Katsuhiko Shirahige Masaru Ishii Takahiro Ochiya Atsushi Miyajima Shuji Terai
author_sort	Suguru Takeuchi
title	Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis
title_short	Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis
title_full	Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis
title_fullStr	Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis
title_full_unstemmed	Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis
title_sort	small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ade7176a775045be931db93405b53155
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Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis

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