2013 Fiscal Year Final Research Report

Generation of the humanized-liver mouse from human iPS cell-derived cholangiocytes

Research Project

Project/Area Number	24700439
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Laboratory animal science
Research Institution	Central Institute for Experimental Animals
Principal Investigator	HIGUCHI Yichiro 公益財団法人実験動物中央研究所, その他部局等, 研究員 (00596281)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	ヒト化肝臓マウス / ヒトiPS細胞 / 胆管上皮細胞 / HepaRG細胞
Research Abstract	Humanized-liver mice, in which the liver has been repopulated with human hepatocytes, have been used to study aspects of human liver physiology such as drug metabolism, toxicology and hepatitis infection. However, the procurement of human hepatocytes is a major problem in producing humanized-liver mice because of the finite nature of the patient-derived resource. In this study, I focused on the cholangiocytes as donor cell source for liver reconstitution since former studies demonstrated the differentiation potential of cholangiocytes (Furuyama et al, Nat. Genet, 2011, Shimper-Ronan et al., Development, 2006). To evaluate the liver reconstitution potential, cholangiocytes that purified from mouse liver, or induced from human iPS cells, were transplanted into the injured liver mouse model. As a result, both of cholangiocytes did not show the liver reconstitution. These results indicate that normal cholangiocytes are not suitable for the donor cell source of humanized-liver mice.