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Potential for clinical applications using human peripheral blood-derived iHep cells

Research Project

Project/Area Number 18K18369
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionKyushu University

Principal Investigator

Udono Miyako  九州大学, 農学研究院, 学術研究員 (30815543)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsiHep細胞 / ダイレクトリプログラミング / 血液 / T細胞 / 末梢血 / H-iHep細胞
Outline of Final Research Achievements

In this study, we aimed to generate human hepatocyte progenitor cells with high proliferative and differentiation potential by direct reprogramming. After re-examining the combination of transcription factors important for liver development, we finally succeeded in generating human iHep cells capable of stable proliferation in long-term culture by introducing three transcription factors (FOXA3, HNF1A, and HNF6) into vascular endothelial cells derived from human umbilical veins and peripheral blood. These cells were found to have the ability to form liver and bile duct tissue-like structures in 3D culture and to differentiate and mature into functional hepatocytes and bile duct epithelial cells, respectively.

Academic Significance and Societal Importance of the Research Achievements

本研究によって開発された方法を用いることで、機能的に成熟した肝細胞や胆管上皮細胞をヒトiHep細胞から大量に増やし臨床での使用および凍結保存が可能になると考えられる。将来的には、肝臓から採取される肝細胞や胆管上皮細胞の代わりにヒトiHep細胞由来の肝細胞・胆管上皮細胞を用いることで、重篤な肝疾患患者に対する新しい移植医療の実現や、個人に応じた薬剤スクリーニングや毒性を評価できるシステムの構築が期待される。

Report

(2 results)
  • 2020 Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2018

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

  • [Journal Article] Cell aggregation culture induces functional differentiation of induced hepatocyte-like cells through activation of Hippo signaling2018

    • Author(s)
      Yamamoto, J., Udono, M., Miura, S., Sekiya, S., Suzuki, A.
    • Journal Title

      Cell Reports

      Volume: 25 Issue: 1 Pages: 183-198

    • DOI

      10.1016/j.celrep.2018.09.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prolonged inhibition of hepatocellular carcinoma cell proliferation by combinatorial expression of defined transcription factors2018

    • Author(s)
      Takashima Yasuo、Horisawa Kenichi、Udono Miyako、Ohkawa Yasuyuki、Suzuki Atsushi
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 11 Pages: 3543-3553

    • DOI

      10.1111/cas.13798

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metformin treatment ameliorates diabetes-associated decline in hippocampal neurogenesis and memory via phosphorylation of insulin receptor substrate 1.2018

    • Author(s)
      Tanokashira D , Kurata E, Fukuokaya W, Kenshiro Kawabe, Takeuchi H,Kashiwada M, Nakazato M , Taguchi A.
    • Journal Title

      FEBS Open Bio

      Volume: 印刷中 Issue: 6 Pages: 914-922

    • DOI

      10.1002/2211-5463.12429

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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