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Title: Human mesenchymal stem cell-engineered hepatic cell sheets accelerate liver regeneration in mice
Authors: Itaba, Noriko
Matsumi, Yoshiaki
Okinaka, Kaori
Ashla, An Afida
Kono, Yohei
Osaki, Mitsuhiko
Morimoto, Minoru
Sugiyama, Naoyuki  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-7633-8495 (unconfirmed)
Ohashi, Kazuo
Okano, Teruo
Shiota, Goshi
Author's alias: 杉山, 直幸
Issue Date: 10-Nov-2015
Publisher: Nature Publishing Group
Journal title: Scientific Reports
Volume: 5
Thesis number: 16169
Abstract: Mesenchymal stem cells (MSCs) are an attractive cell source for cell therapy. Based on our hypothesis that suppression of Wnt/β-catenin signal enhances hepatic differentiation of human MSCs, we developed human mesenchymal stem cell-engineered hepatic cell sheets by a small molecule compound. Screening of 10 small molecule compounds was performed by WST assay, TCF reporter assay, and albumin mRNA expression. Consequently, hexachlorophene suppressed TCF reporter activity in time- and concentration-dependent manner. Hexachlorophene rapidly induced hepatic differentiation of human MSCs judging from expression of liver-specific genes and proteins, PAS staining, and urea production. The effect of orthotopic transplantation of human mesenchymal stem cell-engineered hepatic cell sheets against acute liver injury was examined in one-layered to three-layered cell sheets system. Transplantation of human mesenchymal stem cell-engineered hepatic cell sheets enhanced liver regeneration and suppressed liver injury. The survival rates of the mice were significantly improved. High expression of complement C3 and its downstream signals including C5a, NF-κ B, and IL-6/STAT-3 pathway was observed in hepatic cell sheets-grafted tissues. Expression of phosphorylated EGFR and thioredoxin is enhanced, resulting in reduction of oxidative stress. These findings suggest that orthotopic transplantation of hepatic cell sheets manufactured from MSCs accelerates liver regeneration through complement C3, EGFR and thioredoxin.
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
URI: http://hdl.handle.net/2433/216226
DOI(Published Version): 10.1038/srep16169
PubMed ID: 26553591
Appears in Collections:Journal Articles

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