Development of novel therapy for progressive familial intrahepatic cholestasis using patient-specific iPS cells

• Project/Area Number: 15K19600
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: University of Tsukuba
• Principal Investigator: IMAGAWA Kazuo 筑波大学, 医学医療系, 助教 (40708509)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 黄疸 / 遺伝性肝疾患 / iPS細胞 / 胆汁うっ滞 / 再生医学

Outline of Final Research Achievements

To develop novel therapy for progressive familial intrahepatic cholestasis type 2, we attempted to establish a PFIC2 model by using iPSC technology. We generated the induced pluripotent stem cells from the patients with progressive familial intrahepatic cholestasis type 2. Then, the induced pluripotent stem cells were differentiated into hepatocyte-like cells. The hepatocyte-like cells expressed albumin, and formed bile canaliculi. The biliary excretion capacity of hepatocyte-like cells was impaired. The biliary excretion capacity of the BD-HLCs could be increased by 4PBA treatment. These results suggested that the drug efficacy could be evaluated by using BD-HLCs.

Research Products

• [Journal Article] Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells (2017)
  • Author(s): Imagawa K. 1, Takayama K. 1, Isoyama S., Tanikawa K., Shinkai M., Harada K., Tachibana M., Sakurai F., Noguchi E., Hirata K., Kage M., Kawabata K., Sumazaki R., Mizuguchi H.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 41806-41806
  • DOI: 10.1038/srep41806
  • NAID: 120007135051
  • Peer Reviewed / Open Access
• [Presentation] Splicing analysis using induced pluripotent stem cell-derived hepatocyte-like cells generated from a patient with progressive familial intrahepatic cholestasis type 2 (2016)
  • Author(s): Kazuo Imagawa, Shigemi Isoyama, Ken Tanikawa, Masato Shinkai, Masayoshi Kage, Ryo Sumazaki
  • Organizer: World congress of pediatric gastroenterology, hepatology and nutrition
  • Place of Presentation: Motreal, Canada
  • Year and Date: 2016-10-05
  • Int'l Joint Research
• [Presentation] Human iPSC-derived hepatocyte-like cells generated from patients with bile salt export pump deficiency recapitulate the phenotype of progressive familial intrahepatic cholestasis type 2 (2015)
  • Author(s): Kazuo Imagawa, Kazuo Takayama, Shigemi Isoyama, Ken Tanikawa, Masato Shinkai, Masayoshi Kage, Kenji Kawabata, Ryo Sumazaki, Hiroyuki Mizuguchi
  • Organizer: 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD)
  • Place of Presentation: San Francisco, USA, Moscone West Convention Center
  • Year and Date: 2015-11-13
  • Int'l Joint Research
• [Presentation] 進行性家族性肝内胆汁うっ滞症2型の疾患モデル－iPS細胞由来分化誘導肝細胞を用いた解析－ (2015)
  • Author(s): 今川 和生, 谷川 健, 新開 真人, 鹿毛 政義, 須磨崎 亮
  • Organizer: 第42回日本小児栄養消化器肝臓学会
  • Place of Presentation: 広島、広島国際会議場
  • Year and Date: 2015-10-16
• [Presentation] 進行性家族性肝内胆汁うっ滞症2型のiPS細胞由来分化誘導肝細胞を用いたBSEPスプライシング異常の解析 (2015)
  • Author(s): 今川 和生, 高山 和雄, 磯山 茂美, 谷川 健, 新開 真人, 野口 恵美子, 鹿毛 政義, 川端 健二, 須磨崎 亮, 水口 裕之
  • Organizer: 第32回日本小児肝臓研究会
  • Place of Presentation: 米子、鳥取大学医学部
  • Year and Date: 2015-07-25
• [Presentation] 進行性家族性肝内胆汁うっ滞症2型のiPS細胞由来分化誘導肝細胞を用いた病態再現とフェニル酪酸の薬効評価 (2015)
  • Author(s): 今川 和生, 谷川 健, 鹿毛 政義, 須磨崎 亮
  • Organizer: 第51回日本肝臓学会総会
  • Place of Presentation: 熊本、 ホテル日航熊本
  • Year and Date: 2015-05-21
• [Presentation] 進行性家族性肝内胆汁うっ滞症2型の組織および免疫組織化学所見の多彩性について (2015)
  • Author(s): 谷川 健, 鹿毛 政義, 杉浦 時雄, 今川 和生, 須磨崎 亮, 近藤 礼一郎, 中山 正道, 草野 弘宣, 真田 咲子, 秋葉 純, 小笠原 幸子, 矢野 博久
  • Organizer: 第51回日本肝臓学会総会
  • Place of Presentation: 熊本、 ホテル日航熊本
  • Year and Date: 2015-05-21
• [Presentation] 進行性家族性胆汁うっ滞症2型の疾患特異的iPS細胞を用いた研究 (2015)
  • Author(s): 今川 和生, 高山 和雄, 磯山 茂美, 野口 恵美子, 新開 真人, 立花 雅史, 櫻井 文教, 川端 健二, 須磨崎 亮, 水口 裕之
  • Organizer: 第118回日本小児科学会学術集会
  • Place of Presentation: 大阪、 大阪国際会議場
  • Year and Date: 2015-04-17
• [Presentation] Disease modeling of progressive familial intrahepatic cholestasis type 2 with patient-specific iPSCs derived hepatocyte-like cells (2015)
  • Author(s): Kazuo Imagawa, Kazuo Takayama, Shigemi Isoyama, Emiko Noguchi, Masato Shinkai, Ken Tanikawa, Masayoshi Kage, Masashi Tachibana, Fuminori Sakurai, Kenji Kawabata, Ryo Sumazaki, Hiroyuki Mizuguchi
  • Organizer: 11th Congress of Asian Society for Pediatric Research
  • Place of Presentation: Osaka, Japan, Osaka International Convention Center
  • Year and Date: 2015-04-15
  • Int'l Joint Research