PAI-1 was produced by hepatocyte, and PAI-1 was increased in any portion of liver after hepatectomy. PAI-1 upregulation in the liver was also noted in intestinal adhesion model. This molecular

mechanism also regulates adhesion formation in patients following hepatectomy. These results indicate that the IFN-۷ and PAI-1 are possible therapeutic targets and HGF could prevent postoperative adhesion formation after hepatectomy. Disclosures: The following people have nothing to disclose: Koichiro Ohashi, Tomohiro Yoshimoto, Hisashi Kosaka, Tadamichi Hirano, Yuji Iimuro, Shuhei Nishiguchi, Kenji Nakanishi, Jiro Fujimoto Aims: Human mesenchymal stem cells (hMSCs) have regenerative potential by producing trophic factors as well as hepatic differentiation capacity, and cell-based Ivacaftor therapies utilizing hMSCs are expected to be an

alternative treatment for liver transplantation. For future clinical applications, we focused on Wnt/beta-catenin signal inhibitors since suppression of Wnt/beta-catenin signaling by siRNA enhances hepatic differentiation of hMSCs. In this study, we screened 10 small compounds inhibiting Wnt/beta-catenin signal as candidate compounds driving hMSCs to transdifferentiate into functional hepatocytes, and examined whether cell sheets made from hMSCs by Wnt/beta -catenin signal inhibitors can ameliorate acute liver failure in mice. Methods: First, the effects of Wnt/beta-catenin signal-inhibiting small compounds on TCF4/beta-catenin transcriptional activities were screened by reporter assay in UE7T-13 hMSC cells. Differentiation capacities were assessed by RT-PCR analysis and functional Target Selective Inhibitor Library assays. Cell sheets were fabricated by differentiation procedure on temperature-responsive polymer-grafted culture dishes and then transplanted into NOD/SCID mice. One, two, and three layered cell sheets

were transplanted onto two sites of liver surface in group 1, 2 and 3, respectively and sham operated mice in group 4 were compared as controls. All mice were administrated carbon tetrachloride on day 1. Liver function tests were performed on day 2, 4 and 8, and mice were followed up to day 8. Results: Hexachlorophene potently inhibited TCF4/betacatenin transcriptional activity and enhanced hepatocyte-specific gene expressions, Liothyronine Sodium such as albumin, C3, C4, and APOE. Glycogen storage and urea synthesis were also induced by hexachlorophene. Transplantation of hexachlorophene-induced hepatic cell sheets resulted in significant reduction of serum aminotransferases in group 3, 2, 1 in this order, compared to group 4 on day 4 (P<0. 01, each). Total bilirubin on day 2 was also decreased in group 3, 2 and 1 in this order (P<0. 01, each). Furthermore, survival rate was remarkably improved in group 2 and 3 (P<0. 05). Mitotic and Ki 67-labelled hepatocytes were significantly increased in cell sheets-transplanted mice. RT-PCR analysis showed several human-specific humoral factors such as SCF, HGF, APOE, and C3 were expressed in the graft tissues.