Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis

Abstract Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfol...

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Autores principales:	Hisanori Muto, Takanori Ito, Taku Tanaka, Shinya Yokoyama, Kenta Yamamoto, Norihiro Imai, Yoji Ishizu, Keiko Maeda, Takashi Honda, Tetsuya Ishikawa, Asuka Kato, Taichi Ohshiro, Fumiya Kano, Akihito Yamamoto, Kiyoshi Sakai, Hideharu Hibi, Masatoshi Ishigami, Mitsuhiro Fujishiro
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bcd5f4a38ad5466e8f250c9d66651145
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spelling	oai:doaj.org-article:bcd5f4a38ad5466e8f250c9d666511452021-12-02T18:13:52ZConditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis10.1038/s41598-021-98254-82045-2322https://doaj.org/article/bcd5f4a38ad5466e8f250c9d666511452021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98254-8https://doaj.org/toc/2045-2322Abstract Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α , Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes.Hisanori MutoTakanori ItoTaku TanakaShinya YokoyamaKenta YamamotoNorihiro ImaiYoji IshizuKeiko MaedaTakashi HondaTetsuya IshikawaAsuka KatoTaichi OhshiroFumiya KanoAkihito YamamotoKiyoshi SakaiHideharu HibiMasatoshi IshigamiMitsuhiro FujishiroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hisanori Muto Takanori Ito Taku Tanaka Shinya Yokoyama Kenta Yamamoto Norihiro Imai Yoji Ishizu Keiko Maeda Takashi Honda Tetsuya Ishikawa Asuka Kato Taichi Ohshiro Fumiya Kano Akihito Yamamoto Kiyoshi Sakai Hideharu Hibi Masatoshi Ishigami Mitsuhiro Fujishiro Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis
description	Abstract Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α , Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes.
format	article
author	Hisanori Muto Takanori Ito Taku Tanaka Shinya Yokoyama Kenta Yamamoto Norihiro Imai Yoji Ishizu Keiko Maeda Takashi Honda Tetsuya Ishikawa Asuka Kato Taichi Ohshiro Fumiya Kano Akihito Yamamoto Kiyoshi Sakai Hideharu Hibi Masatoshi Ishigami Mitsuhiro Fujishiro
author_facet	Hisanori Muto Takanori Ito Taku Tanaka Shinya Yokoyama Kenta Yamamoto Norihiro Imai Yoji Ishizu Keiko Maeda Takashi Honda Tetsuya Ishikawa Asuka Kato Taichi Ohshiro Fumiya Kano Akihito Yamamoto Kiyoshi Sakai Hideharu Hibi Masatoshi Ishigami Mitsuhiro Fujishiro
author_sort	Hisanori Muto
title	Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis
title_short	Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis
title_full	Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis
title_fullStr	Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis
title_full_unstemmed	Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis
title_sort	conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates nash via the gut-liver axis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bcd5f4a38ad5466e8f250c9d66651145
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Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis

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