Development of humanized-liver mice using hepatocyte derived from pediatric liver/biliary tract diseases and investigation of pathological mechanism of liver/biliary tract diseases.

2013 Fiscal Year Final Research Report

• Project/Area Number: 24650244
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Laboratory animal science
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: TANOUE Akito 独立行政法人国立成育医療研究センター, 薬剤治療研究部, 部長 (60301800)
• Research Collaborator: NAKAMURA Kazuaki 独立行政法人国立成育医療研究センター, 研究所薬剤治療研究部・実験薬理研究室, 室長 (80392356)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 疾患モデル / ヒト肝型マウス / 胆道閉鎖症

Research Abstract

In this study, we tried for development of humanized-liver mice in which the liver is reconstitute with human hepatocyte derived from some liver/biliary tract diseases. We demonstrated that we could produce some humanized-liver mice which have disease derived hepatocyte. Especially, we tried for producing humanized-liver using hepatocyte derived from biliary atresia. We showed that hepatocyte derived from biliary atresia produced human albumin and expressed drug metabolism enzymes in mouse liver. These results indicated that hepatocytes have normal hepatic functions even in biliary atresia. The results of this study indicated the possibility for development of humanized-disease liver mice and these mice may be useful for investigating pathological mechanism of liver/biliary tract diseases.

Research Products

• [Journal Article] Hepatocyte transplantation using the living donor reduced-graft in a baby with ornithine transcarbamylase deficiency : a novel source for hepatocytes (2014)
  • Author(s): Enosawa S, Horikawa R, Yamamoto A, Sakamoto S, Shigeta T, Nosaka S, Fujimoto J, Tanoue A, Nakamura K, Umezawa A, Matsubara Y, Matsui A, Kasahara M.
  • Journal Title: Liver Transplantation Volume: 20 Pages: 391-393
  • DOI: 10.1002/lt.23800
  • Peer Reviewed
• [Journal Article] Etiology of biliary atresia as a developmental anomaly : Recent advances (2013)
  • Author(s): Nakamura K, Tanoue A.
  • Journal Title: Journal of Hepato-Biliary-Pancreatic Sciences Volume: 20(5) Pages: 459-464
  • DOI: 10.1007/s00534-013-0604-4
  • Peer Reviewed
• [Journal Article] Expression of albumin and cytochrome P450 enzymes in HepG2 cells cultured with a nanotechnology-based culture plate with microfabricated scaffold (2011)
  • Author(s): Nakamura K, Kato N, Aizawa K, Mizutani R, Yamauchi J, Tanoue A.
  • Journal Title: Journal of Toxicological Science Volume: 36 Pages: 625-633
  • DOI: 10.2131/jts.36.625
  • Peer Reviewed
• [Journal Article] 胆道閉鎖症の病因に関する最近の知見-特に発生異常説に関して- (2011)
  • Author(s): 中村和昭、田上昭人
  • Journal Title: Organ Biology Volume: 18 (3) Pages: 5-10
  • Peer Reviewed
• [Journal Article] Hepatocytes buried in the cirrhotic livers of biliary atresia patients proliferate and function in the liver of uPA-NOG mice
  • Author(s): Suemizu H, Nakamura K, Kawai K, Higuchi Y, Kasahara M, Fujimoto J, Tanoue A, Nakamura M. contributed equally to this work
  • Journal Title: Liver Transplantation Volume: (In press)
  • DOI: 10.1002/lt.23916
  • Peer Reviewed
• [Presentation] HEPATOCYTES TRANSPLANTATION FOR AN INFANT OF ORNITHINE TRANSCARBAMYLASE DEFICIENCY USING CELLS ISOLATED FROM LIVING DONOR REDUCED-GRAFT TISSUE (2014)
  • Author(s): Matsui A, Horikawa R, Yamamoto A, Sakamoto S, Shigeta T, Nosaka S, Fujimoto J, Tanoue A, Nakamura K, Umezawa A, Matsubara Y, Kasahara M.
  • Organizer: 47th Annual Meeting of The European Society for Paediatric Gastroenterology, Hepatology and Nutrition
  • Place of Presentation: The Jerusalem International Convention Center
  • Year and Date: 20140609-12
• [Presentation] IN VITRO DRUG METABOLITE PROFILING USING HUMAN HEPATOCYTES FRESHLY ISOLATED FROM TRANSPLANT DONORS (2011)
  • Author(s): Tanaka K, Nakamura K, Nozaki K, Terashita A, Tanoue A, Teramura T.
  • Organizer: 第26回日本薬物動態学会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 20111116-18