Study on establishment of experimental animal model for chimeric liver with hepatitis C virus infection using induced hepatocyte-like cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590959
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: AZUMA Seishin 東京医科歯科大学, 医学部附属病院, 助教 (10376783)
• Co-Investigator(Kenkyū-buntansha): KAKINUMA Sei 東京医科歯科大学, 大学院医歯学総合研究科, 寄付講座講師 (30372444) ; ASAHINA Yasuhiro 東京医科歯科大学, 大学院医歯学総合研究科, 寄付講座教授 (00422692) ; WATANABE Mamoru 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10175127)
• Co-Investigator(Renkei-kenkyūsha): SAKAMOTO Naoya 北海道大学, 医学研究科, 教授 (10334418)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 移植 / 発生・分化 / 再生医学 / 肝疾患治療 / 細胞・組織

Outline of Final Research Achievements

Investigators of this research project have studied on the molecular mechanisms regulating differentiation and proliferation of hepatic stem/progenitor cells. Based on the results of above-mentioned analysis, we tried to establish the mouse model of chimeric liver using directly reprogrammed hepatocyte-like cells. We found that Wnt5a and Wnt5a-related molecules control the biliary differentiation of hepatic stem/progenitor cells. Next, our data indicated that MMP14 and MMP14-related molecules regulate luminal formation of bile ducts in developing liver, and that expression of MMP14 improves the efficacy of transplantation using hepatic stem/progenitor cells. These studies contribute to the progress of drug discovery for viral hepatitis using mouse model of cell-transplanted chimeric liver in future.

Free Research Field

消化器病学