Reconstitution of human hepatic cells in decellularized rodent liver

• Project/Area Number: 25670589
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Osaka City University
• Principal Investigator: IKEDA Kazuo 大阪市立大学, 大学院医学研究科, 教授 (80275247)
• Co-Investigator(Renkei-kenkyūsha): YOSHIZATO Katsutoshi 大阪市立大学, 大学院医学研究科, 客員教授 (20095516)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肝細胞 / 肝星細胞 / iPS細胞 / 肝臓基質

Outline of Final Research Achievements

Hepatocytes induced from human iPS cells are expected to have medical applications such as biomedical research, drug study and regenerative medicine. In the present study, we first tried to induce hepatic-like cells from human iPS cells by using human hepatic stellate cells. Next, decellularized liver (DCL) was generated. Each mouse or rat liver was perfused sequentially with phosphate buffer saline, sodium dodecyl sulfate and TritonX100 through portal vein. Hepatic-like cells from human iPS cells and human hepatic stellate cells were infused through a portal vein after the completion of the decellularized procedure and cultured. When expression level of albumin and cyp3A4 was measured, the expression in the cells cultured in DCL was not significantly increased, compared with that in the cells cultured in normal dish. We need further devices to enhance the expression.

Research Products

• [Journal Article] Efficient engraftmentof human iPS cell-derived hepatocyte-like cells in uPA/SCID mice by overexpression of FNK, a Bcl-x(L)mutant gene. (2015)
  • Author(s): Nagamoto Y, Takayama K, Tashiro K, Tateno C, Sakurai F, Tachibana M, Kawabata K, Ikeda K, Tanaka Y, Mizuguchi H.
  • Journal Title: Cell Transplant. Volume: 24 Pages: 1127-1138
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Involvement of hepatic stellate cell cytoglobin in acute hepatocyte damage through the regulation of CYP2E1-mediated xenobiotic metabolism. (2015)
  • Author(s): Teranishi Y, Matsubara T, Krausz KW, Le TT, Gonzalez FJ, Yoshizato K, Ikeda K, Kawada N
  • Journal Title: Lab Invest Volume: 95 Issue: 5 Pages: 515-524
  • DOI: 10.1038/labinvest.2015.29
  • Peer Reviewed
• [Journal Article] Cilostazol attenuates hepatic stellate cell activation and protects mice against carbon tetrachloride-induced liver fibrosis (2014)
  • Author(s): Saito S, Hata K, Iwaisako K, Yanagida A, Takeiri M, Tanaka H, Kageyama S,Hirao H,Ikeda K, Asagiri M, Uemoto S.
  • Journal Title: Hepatol Res. Volume: In press
  • NAID: 120005625637
  • Peer Reviewed
• [Journal Article] Efficient engraftment of human iPS cell-derived hepatocyte-like cells in uPA/SCID mice by overexpression of FNK, a Bcl-xL mutant gene. (2014)
  • Author(s): Nagamoto Y., Takayama K., Tashiro K., Tateno C., Sakurai F., Tachibana M., Kawabata K., Ikeda K., Tanaka Y., Mizuguchi H.
  • Journal Title: Cell Transplantation Volume: In press
  • Peer Reviewed
• [Presentation] Characterization of senescence-associated hepatic stellate cells using human primary culture cells (2015)
  • Author(s): Odagiri N., Matsubara T., Kawada N., Ikeda K.
  • Organizer: 18th INTERNATIONAL SYMPOSIUM ON CELLS OF THE HEPATIC SINUSOID
  • Place of Presentation: Asilomar, California, USA
  • Year and Date: 2015-11-11
  • Int'l Joint Research
• [Presentation] Enhanced endoplasmic reticulum stress response has a protective role in acetaminophen-induced liver injury in mice (2015)
  • Author(s): Sogabe N., Matsubara T., Teranishi Y., Nakatani K., Kawada N., Ikeda K.
  • Organizer: 18th INTERNATIONAL SYMPOSIUM ON CELLS OF THE HEPATIC SINUSOID
  • Place of Presentation: Asilomar, California, USA
  • Year and Date: 2015-11-11
  • Int'l Joint Research
• [Presentation] Over-expression of Bcl-xl mutant (FNK) improves the engraftment efficacy of human iPS cell-derived hepatocytes in the liver of uPA/SCID mice (2013)
  • Author(s): Nagamoto Y, Takayama K, Tashiro K, Tateno C, Sakurai F, Tachibana K, Ikeda K, Tanaka Y, Mizuguchi H.
  • Organizer: The 20th Annual Meeting of the Japanese Society for the Research of Hepatic Cells
  • Place of Presentation: 大阪国際会議場