OKANO Teruo
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position  
Article types Original article
Language English
Peer review Peer reviewed
Title Human mesenchymal stem cell-engineered hepatic cell sheets accelerate liver regeneration in mice.
Journal Formal name：Scientific reports
Abbreviation：Sci Rep
ISSN code：20452322/20452322
Domestic / ForeginForegin
Volume, Issue, Page 5,pp.16169
Author and coauthor ITABA Noriko†, MATSUMI Yoshiaki, OKINAKA Kaori, ASHLA An Afida, KONO Yohei, OSAKI Mitsuhiko, MORIMOTO Minoru, SUGIYAMA Naoyuki, OHASHI Kazuo, OKANO Teruo, SHIOTA Goshi
Publication date 2015/11
Summary 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