Evaluation of the inhibited hepatic sinusoidal regeneration after hepatectomy in cirrhotic liver and attempt for promoting liver regeneration using endothelial progenitor cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591994
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Chiba University
• Principal Investigator: SHIMIZU Hiroaki 千葉大学, 医学(系)研究科(研究院), 准教授 (80272318)
• Co-Investigator(Kenkyū-buntansha): MIYAZAKI Masaru 千葉大学, 大学院医学研究院, 教授 (70166156) ; OHTSUKA Masayuki 千葉大学, 大学院医学研究院, 講師 (90334185) ; KUBOKI Satoshi 千葉大学, 医学部附属病院, 助教 (50571410) ; KIMURA Fumio 千葉大学, 大学院医学研究院, 教授 (70334208)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肝再生 / 黄疸 / 肝硬変 / 肝類洞 / 血管内皮前駆細胞

Outline of Final Research Achievements

Hepatic TGF-β1 mRNA levels increased in both cholestatic and cirrhotic rats. HGF and VEGF also tended to increase. In cell isolates, TGF-β1 mRNA was found mainly in hepatic stellate cell (HSC) fraction. Immunohistochemical study revealed increased number of HSCs (desmin-positive cells) and activated HSCs (α-SMA-positive cells) in portal areas with length of cholestasis. In 70% hepatectomy model, liver regeneration was delayed. TGF-β1 mRNA was significantly upregulated and earlier peak of HGF mRNA was lost. Cholestatic or cirrhotic liver induces HSC proliferation and activation, leading to upegulation of TGF-β1 mRNA expression and suppression of HGF and VEGF mRNA expression. These altered expression pattern may be strongly involved in delayed hepatic sinusoidal regeneration. Next, we have tried to isolate endothelial progenitor cells using FACS, but failed to obtain the expected amount of the CD34 cells. Thus, we planed to use bone marrow cell in portal administration

Free Research Field

医歯薬学