Establishment of a new method of inducing differentiation from human embryonic stem cells to hepatocytes in vitro and investigation of the clinical utility for cell transplantation.

• Project/Area Number: 20390356
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyoto University
• Principal Investigator: IKAI Iwao Kyoto University, 医学研究科, 非常勤講師 (60263084)
• Co-Investigator(Kenkyū-buntansha): YASUCHIKA Kentaro 京都大学, 医学研究科, 病院特定助教 (00378895) ; ISHII Takamichi 京都大学, 医学研究科, 医員 (70456789) ; 上本 伸二 京都大学, 医学研究科, 教授 (40252449) ; 加茂 直子 京都大学, 医学研究科, 医員 (50452355) ; 波多野 悦朗 京都大学, 医学研究科, 助教 (80359801)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2009: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2008: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: ヒトES細胞 / 分化誘導 / 肝細胞 / 細胞移植 / ヒトiPS細胞

Research Abstract

We demonstrated that human embryonic stem cells (hESCs) matured into hepatocyte-like cells with higher hepatocyte function in vitro via co-culturing with the fetal murine hepatic cells after administration of hepatocyte growth factor (HGF) and ActivinA. Furthermore, we also demonstrated that human induced pluripotent stem cells (hiPSCs) could be differentiated into hepatocyte-like cells. Moreover, we suggested that transplantation of mature hepatocytes for acute liver failure significantly improved the survival rate in comparison to that of transplantation of immature cells.

Research Products

• [Journal Article] A transmembrane glycoprotein, gp 38, is a novel marker for immature hepatic progenitor cells in fetal mouse livers. (2011)
  • Author(s): 小西小百合、安近健太郎, ほか
  • Journal Title: In vitro Cellular & Developmental biology.Animal Volume: 47 Pages: 45-53
  • Peer Reviewed
• [Journal Article] In vitro hepatic aturation of human embryonic stem cells by using a mesenchymal cell line derived from murine fetal livers (2010)
  • Author(s): 石井隆道、安近健太郎、福光剣、猪飼伊和夫
  • Journal Title: Cell Tissue Research Vo1.339, No.3 Pages: 505-512
  • Peer Reviewed
• [Journal Article] In vitro hepatic maturation of human embryonic stem cells by using a mesenchymal cell line derived from murine fetal livers. (2010)
  • Author(s): 石井隆道、安近健太郎, ほか
  • Journal Title: Cell Tissue Research Volume: 339 Pages: 505-512
  • NAID: 120002511339
  • Peer Reviewed
• [Journal Article] In vitro hepatic maturation of human embryonic stem cells by using a mesenchymal cell line derived from murine fetal livers (2010)
  • Author(s): Ishii T, et al
  • Journal Title: Cell Tissue Research Mar; 339(3) Pages: 505-512
  • NAID: 120002511339
  • Peer Reviewed
• [Journal Article] Establishment of a cell line derived from a mouse fetal liver that has the characteristic to promote the hepatic maturation of mouse embryonic stem cells by a coculture method, Tissue Engineering. (2009)
  • Author(s): 福光剣、石井隆道、安近健太郎、猪飼伊和夫
  • Journal Title: Part A Vo1.15、No.12 Pages: 3847-3856
  • Peer Reviewed
• [Journal Article] Establishment of a cell line derived from a mouse fetal liver that has the characteristic to promote the hepatic maturation of mouse embryonic stem cells by a coculture method (2009)
  • Author(s): Fukumitsu K, et al
  • Journal Title: Tissue Engineering Dec; 15(12) Pages: 3847-3856
  • Peer Reviewed
• [Journal Article] Effects of extracellular matrixes and growth factors on the hepatic differentiation of human embryonic stem cells, American Journal of Physiology. (2008)
  • Author(s): 石井隆道、福光剣、安近健太郎、猪飼伊和夫
  • Journal Title: Gastrointestine and Liver physiology Vo1.295、No.2 Pages: 313-321
  • Peer Reviewed
• [Journal Article] Effects of extracellular matrixes and growth factors on the hepatic differentiation of human embryonic stem cells (2008)
  • Author(s): Ishii T, et. al.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol. 295(2) Pages: 313-321
  • Peer Reviewed
• [Presentation] 致死性急性肝障害モデルマウスに対する細胞移植における、移植細胞の分化段階による治療効果の比較検討 (2010)
  • Author(s): 上村良, ら
  • Organizer: 日本再生医療学会
  • Place of Presentation: 広島
  • Year and Date: 2010-03-17
• [Presentation] Variation in hepatic differentiation propensity among human induced pluripotent stem cell (iPSC) lines (2010)
  • Author(s): 梶原正俊、石井隆道、猪飼伊和夫、上本伸二、山中伸弥
  • Organizer: The 8th International Society for Stem CellResearch (ISSCR)
  • Place of Presentation: San Francisco, U.S.A
• [Presentation] Comparative study of transplantation of cells at various differentitation stages into mice withinduced lethal liver damage (2010)
  • Author(s): 上村良、石井隆道、安近健太郎、猪飼伊和夫
  • Organizer: 第45回欧州肝臓学会議(EASL)
  • Place of Presentation: ウィーン、オーストリア
• [Presentation] Comparative study of transplantation of cells at various differentiation stages into mice with induced lethal liver damage (2010)
  • Author(s): 上村良、石井隆道, ほか
  • Organizer: 第45回欧州肝臓学会議(EASL)
  • Place of Presentation: ウィーン(オーストリア)
• [Presentation] Variation in hepatic differentiation propensity among human induced pluripotent stem cell (iPSC) lines (2010)
  • Author(s): 梶原正俊、上本伸二, ほか
  • Organizer: The 8th International Society for Stem Cell Research (ISSCR)
  • Place of Presentation: San Francisco(U.S.A.)
• [Presentation] The effect of extracellular matrices and growth factors on hepatic lineage differentiation of human embryonic stem cells (2008)
  • Author(s): Fukumitsu K et. al
  • Organizer: Digestive Disease Week 2008
  • Place of Presentation: San Diego、USA
  • Year and Date: 2008-05-20