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

Research Project

Project/Area Number 15K19600
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Research InstitutionUniversity 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 *help
¥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.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (9 results)

All 2017 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells2017

    • 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

    • Related Report
      2016 Annual Research Report
    • 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 22016

    • 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
    • Related Report
      2016 Annual Research Report
    • 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 22015

    • 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
    • Related Report
      2015 Research-status Report
    • 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
    • Related Report
      2015 Research-status Report
  • [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
    • Related Report
      2015 Research-status Report
  • [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
    • Related Report
      2015 Research-status Report
  • [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
    • Related Report
      2015 Research-status Report
  • [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
    • Related Report
      2015 Research-status Report
  • [Presentation] Disease modeling of progressive familial intrahepatic cholestasis type 2 with patient-specific iPSCs derived hepatocyte-like cells2015

    • 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
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2018-03-22  

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