Differentiation of human induced pluripotent stem cells to hepatocyte lineage

• Project/Area Number: 15K09032
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: 独立行政法人国立病院機構 下志津病院(臨床研究部)
• Principal Investigator: Tomizawa Minoru 独立行政法人国立病院機構 下志津病院(臨床研究部), 臨床研究部, その他 (90334193)
• Co-Investigator(Renkei-kenkyūsha): OHIRA Miki 千葉県がんセンター(研究所), がんゲノム研究室, 室長 (20311384)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: iPS細胞 / 肝細胞 / ブドウ糖 / アルギニン / 乳酸 / 糖新生 / 尿素サイクル / Coriサイクル / 肝細胞分化 / 解糖系 / 転写因子 / ガラクトース / オルニチン

Outline of Final Research Achievements

To promote differentiation of human induced pluripotens stem (iPS) cells to hepatocytes, oncostati M, and M50054 were added to a medium without glucose or arginine, and added with galactose and ornithine (hepatocyte differentiation inducer). The expression levels of alpha-feto protein were up-regulated in iPS cells cultured in HDI for 2 days. It was suggested that HDI promoted differentiation of iPS cells to hepatocyte lineage.

Research Products

• [Journal Article] Oncostatin M in William’s E medium is suitable for initiation of hepatocyte differentiation in human induced pluripotent stem cells (2017)
  • Author(s): Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Ishige N
  • Journal Title: Mol Med Rep Volume: 15 Issue: 5 Pages: 3088-3092
  • DOI: 10.3892/mmr.2017.6406
  • Peer Reviewed
• [Journal Article] 2-Deoxy-D-glucose potentially initiates hepatocyte differentiation of human induced pluripotent stem cells (2017)
  • Author(s): Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Ishige N
  • Journal Title: Mol Med Rep Volume: 15 Issue: 5 Pages: 3083-3087
  • DOI: 10.3892/mmr.2017.6405
  • Peer Reviewed
• [Journal Article] Differentiation of human induced pluripotent stem cells in Williams’ E initiation medium supplemented with 3-bromopyruvate and 2-deoxy-D-glucose (2017)
  • Author(s): Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Ishige N
  • Journal Title: Mol Med Rep Volume: 15 Issue: 6 Pages: 3719-3723
  • DOI: 10.3892/mmr.2017.6474
  • Peer Reviewed
• [Journal Article] Improved survival and initiation of differentiation of human induced pluripotent stem cells to hepatocyte-like cells upon culture in William’s E medium followed by hepatocyte differentiation inducer treatment. (2016)
  • Author(s): Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Ishige N.
  • Journal Title: PLoS One Volume: 11
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Transcription factors and medium suitable for initiating the differentiation of human induced pluripotent stem cells to the hepatocyte lineage (2016)
  • Author(s): Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Ishige N.
  • Journal Title: J Cell Biochem Volume: 117 Pages: 2001-2009
  • Acknowledgement Compliant
• [Journal Article] An optimal medium supplementation regimen for initiation of hepatocyte differentiation in human induced pluripotent stem cells (2015)
  • Author(s): Tomizawa M, Shinozaki F, Hasegawa R, Fugo K, Shirai Y, Motoyoshi Y, Sugiyama T, Yamamoto S, Kishimoto T, Ishige N
  • Journal Title: J Cell Biochem Volume: 116 Issue: 8 Pages: 1479-1489
  • DOI: 10.1002/jcb.25139
  • Peer Reviewed
• [Journal Article] Involvement of Wnt pathway in feeder-free culture of human induced pluripotent stem cells (2015)
  • Author(s): Tomizawa M, Shinozaki, F, Motoyoshi, Y, Sugiyama, T, Shigenori Yamamoto, S, Ishige, N
  • Journal Title: Mol Med Rep Volume: 12 Issue: 5 Pages: 6797-6800
  • DOI: 10.3892/mmr.2015.4314
  • Peer Reviewed
• [Presentation] iPS細胞から肝細胞への分化を促進する転写因子 (2018)
  • Author(s): 富澤稔、篠崎文信、本吉慶史、杉山隆夫、山本重則、石毛尚起
  • Organizer: 第17回日本再生医療学会
• [Presentation] iPS細胞から肝細胞への分化を促進する転写因子の解明 (2017)
  • Author(s): 富澤稔、篠崎文信、本吉慶史、杉山隆夫、山本重則、石毛尚起
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 東北大学
  • Year and Date: 2017-03-07
  • Int'l Joint Research
• [Presentation] iPS細胞から肝細胞への分化を誘導する転写因子 (2017)
  • Author(s): 富澤稔、篠崎文信、本吉慶史、杉山隆夫、山本重則、石毛尚起
  • Organizer: 103回日本消化器病学会総会
• [Presentation] Transcription factors and medium suitable for initiating the differentiation of human induced pluripotent stem cells to the hepatocyte lineage (2017)
  • Author(s): Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Ishige N
  • Organizer: 15th Annual Meeting of International Society of Stem Cell Research (ISSCR)
  • Int'l Joint Research
• [Presentation] iPS細胞から肝細胞への分化を促進する転写因子群の解明 (2016)
  • Author(s): 富澤稔、篠崎文信、本吉慶史、杉山隆夫、山本重則、石毛尚起
  • Organizer: 第20回日本肝臓学会大会
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2016-11-03
• [Presentation] Human induced pluripotent stem cells survived and initiated hepatocyte differentiation in William’s E medium followed by hepatocyte differentiation inducer (2016)
  • Author(s): 7.Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Ishige N
  • Organizer: 14th Annual Meeting of International Society of Stem Cell Research (ISSCR)
  • Place of Presentation: Moscone West, San Francisco, CA, USA
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] iPS細胞から肝細胞への分化を促進する培地の開発 (2016)
  • Author(s): 富澤稔、篠崎文信、本吉慶史、杉山隆夫、山本重則、石毛尚起
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2016-03-17
• [Presentation] iPS細胞から肝細胞への分化を促進する培地の開発 (2015)
  • Author(s): 富澤稔、篠崎文信、本吉慶史、杉山隆夫、山本重則、石毛尚起
  • Organizer: 第19回日本肝臓学会大会
  • Place of Presentation: 品川
  • Year and Date: 2015-10-08
• [Presentation] An optimal medium supplementation regimen for initiation of hepatocyte differentiation in human induced pluripotent stem cells (2015)
  • Author(s): 15.Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Ishige N
  • Organizer: 13th Annual Meeting of International Society of Stem Cell Research
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2015-06-24
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] 肝細胞系譜細胞の製造方法、該製造方法で得られた肝細胞系譜細胞又は培養物、並びに肝細胞分化誘導培地 (2017)
  • Inventor(s): 富澤 稔
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-211334
  • Filing Date: 2017