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

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ヒト化肝臓マウス / ヒトiPS細胞 / 胆管上皮細胞 / HepaRG細胞 / 肝臓 / ヒト肝蔵マウス

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.

Research Products

• [Journal Article] A Novel Enhanced Green FluorescentProtein-Expressing NOG Mouse for Analyzingthe Microenvironment of Xenograft Tissues (2014)
  • Author(s): Yuichiro Higuchi, Kenji Kawai, Masafumi Yamamoto, Miyuki Kuronuma, Yasuhiko Ando, Ikumi Katano, Masato Nakamura, Hiroshi Suemizu
  • Journal Title: Experimental Animals Volume: 63 Issue: 1 Pages: 55-62
  • DOI: 10.1538/expanim.63.55
  • NAID: 130003391611
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed / Open Access
• [Journal Article] The human hepatic cell line HepaRG cells, possible cell source for steady generation of humanized liver TK-NOG mice (2014)
  • Author(s): Higuchi, Y., Kawai, K., Yamazaki, H., Nakamura, M., Bree, F., Guillouzo, C., and Suemizu, H.
  • Journal Title: Xenobiotica Volume: 27 Issue: 2 Pages: 146-157
  • DOI: 10.3109/00498254.2013.836257
  • Peer Reviewed
• [Presentation] HepaRG細胞を用いたヒト化肝臓マウスの作成 (2014)
  • Author(s): 樋口裕一郎、川井健司、山崎洋志、中村雅登、Franxoise Bree, Christiane Guguen-Guillouzo、末水洋志
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] HepaRG細胞を用いたヒト化肝臓マウスの作成 (2014)
  • Author(s): 樋口裕一郎、川井健司、山崎洋志、中村雅登、Francoise Bree、Christiane Guguen-Guilllouzo、末水洋志
  • Organizer: 第１３回日本再生医療学会総会
  • Place of Presentation: 国立京都国際会館