オカノ　テルオ   OKANO Teruo   岡野　光夫    所属   研究施設 研究施設    職種   特任顧問
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Human mesenchymal stem cell-engineered hepatic cell sheets accelerate liver regeneration in mice.
掲載誌名	正式名：Scientific reports 略　 称：Sci Rep ISSNコード：20452322/20452322
掲載区分	国外
巻・号・頁	5,pp.16169
著者・共著者	ITABA Noriko†, MATSUMI Yoshiaki, OKINAKA Kaori, ASHLA An Afida, KONO Yohei, OSAKI Mitsuhiko, MORIMOTO Minoru, SUGIYAMA Naoyuki, OHASHI Kazuo, OKANO Teruo, SHIOTA Goshi
発行年月	2015/11
概要	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-κB, 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.
DOI	10.1038/srep16169
PMID	26553591