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Development of the core technologies of regenerative therapy with human somatic stem cells for cirrhosis and liver failure

Research Project

Project/Area Number 18H02866
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Zheng Yun-Wen  筑波大学, 医学医療系, 客員研究員 (80404995)

Co-Investigator(Kenkyū-buntansha) 大河内 信弘  筑波大学, 医学医療系, 客員教授 (40213673)
高井 まどか  東京大学, 大学院工学系研究科(工学部), 教授 (40287975)
高橋 一広  筑波大学, 医学医療系, 講師 (80794528)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywordsオルガノイド / 肝不全 / 再生医療 / 細胞移植 / ヒト体性幹細胞 / 免疫不全ラット / ヒト化肝臓 / ヒト化ラット
Outline of Final Research Achievements

In this study, we developed an original technology to create novel digestive organoids by using a novel three-dimensional multicellular co-culture system for human placental tissue stem cells and human pluripotent stem cells to mimic the organogenesis process and cell-society interactions in vivo. Furthermore, by transplanting human hepatocytes into immunodeficient rats, it is confirmed human albumin secretion and human-type drug metabolism. We also confirmed the role of macrophages in human-rat xeno-rejection. By expressing the "don't eat me" gene, which induces immune tolerance to human cells, in rats, we can create a new transplantation model that is neither cell transplantation nor organ transplantation, and is expected to make a significant contribution to transplantation medicine and regenerative medicine in the future.

Academic Significance and Societal Importance of the Research Achievements

免疫不全動物を用いて、異種移植におけるマクロファージの種差認識と拒絶に関わる役割の深く理解できたことは、器官移植医療における器官源の作成や移植効率向上に向けた基盤的技術につながると考えられる。また、肝オルガノイドの作成と移植は、消化器系の難治性疾患であり年間死者数が2万人に及ぶ末期肝不全に対する新規治療法となるものである。さらに、この移植・再生医療の新規基盤は、他臓器のオルガノイド移植、ヒト化動物モデルの作成、創薬などの、一連の新しい治療のフロンティアとなりうるものである。

Report

(3 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2018 Annual Research Report

Research Products

(23 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (11 results) (of which Int'l Joint Research: 2 results) Book (2 results) Funded Workshop (1 results)

  • [Int'l Joint Research] 中国科学院上海生命科学研究院/江蘇大学(中国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] 中国科学院上海生命科学研究院/江蘇大学(中国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Hepatic stellate cells contribute to liver regeneration through galectins in hepatic stem cell niche2020

    • Author(s)
      Ge Jian-Yun, Zheng Yun-Wen, Tsuchida Tomonori, Furuya Kinji, Isoda Hiroko, Taniguchi Hideki, Ohkohchi Nobuhiro, Oda Tatsuya
    • Journal Title

      Stem Cell Research & Therapy

      Volume: 11 Pages: 425-425

    • DOI

      10.1186/s13287-020-01942-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Practical choice for robust and efficient differentiation of human pluripotent stem cells2020

    • Author(s)
      Fang Mei, Liu Li-Ping, Zhou Hang, Li Yu-Mei, Zheng Yun-Wen
    • Journal Title

      World Journal of Stem Cells

      Volume: 12 Pages: 752-760

    • DOI

      10.4252/wjsc.v12.i8.752

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A potential ex vivo infection model of human induced pluripotent stem cell-3D organoids beyond coronavirus disease 20192020

    • Author(s)
      Zhou H, Liu LP, Fang M, Li YM, Zheng YW
    • Journal Title

      Histol Histopathol

      Volume: 35 Pages: 1077-82

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation2019

    • Author(s)
      Liu Li-Ping、Li Yu-Mei、Guo Ning-Ning、Li Shu、Ma Xiaolong、Zhang Yi-Xuan、Gao Yimeng、Huang Jian-Ling、Zheng Dong-Xu、Wang Lu-Yuan、Xu Hui、Hui Lijian、Zheng Yun-Wen
    • Journal Title

      Cell Reports

      Volume: 27

    • DOI

      10.1016/j.celrep.2019.03.046

    • NAID

      120007128261

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recapitulation of hepatitis B virus?host interactions in liver organoids from human induced pluripotent stem cells2018

    • Author(s)
      Nie Yun-Zhong、Zheng Yun-Wen、Miyakawa Kei、Murata Soichiro、Zhang Ran-Ran、Sekine Keisuke、Ueno Yasuharu、Takebe Takanori、Wakita Takaji、Ryo Akihide、Taniguchi Hideki
    • Journal Title

      EBioMedicine

      Volume: 35 Pages: 114-123

    • DOI

      10.1016/j.ebiom.2018.08.014

    • NAID

      120007128498

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of Individualized Induced Pluripotent Stem Cells From Fibroblasts of Keloid Lesions in Patients2018

    • Author(s)
      Zhang Y.-X.、Liu L.-P.、Li M.、Huang J.-L.、Xu H.、Chen X.-D.、Zhu W.-Y.、Cai Y.-P.、Guo N.-N.、Chen Z.-Q.、Zheng Y.-W.、Li Y.-M.
    • Journal Title

      Transplantation Proceedings

      Volume: 50 Pages: 2868-2871

    • DOI

      10.1016/j.transproceed.2018.04.008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Multiple-Cell Microenvironment in a 3-Dimensional System Enhances Direct Cellular Reprogramming Into Hepatic Organoids2018

    • Author(s)
      Wang L.-Y.、Liu L.-P.、Ge J.-Y.、Yuan Y.-Y.、Sun L.-L.、Xu H.、Huang P.-Y.、Hui L.-J.、Isoda H.、Ohkohchi N.、Li Y.-M.、Zheng Y.-W.
    • Journal Title

      Transplantation Proceedings

      Volume: 50 Pages: 2864-2867

    • DOI

      10.1016/j.transproceed.2018.03.076

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Chimeric liver with human hepatocytes in rats2021

    • Author(s)
      葛剣云、張魯狄、古屋欽司、大河内信弘、惠利健、小田竜也、鄭允文
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Potential of amniotic epithelial cells for skin reconstitution and its reprogramming2021

    • Author(s)
      Li-Ping Liu, Dong-Xu Zheng, Yun-Wen Zheng
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 臍帯血単核細胞を用いたヒト-ラット異種移植におけるマクロファージの影響2020

    • Author(s)
      古屋欽司、鄭允文、梁宸、古田智章、葛剣云、八木洋也、濱田洋実、礒田博子、小田竜也
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Galectins from hepatic stellate cells in hepatic stem cell niche contribute to liver regeneration2020

    • Author(s)
      Ge JY, Tsuchida T, Oda T, Taniguchi H, Zheng YW
    • Organizer
      2020 Annual Meeting of International Society for Stem Cell Research
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 胎盤組織由来体性幹細胞を用いた三次元多細胞共培養法による肝性分化誘導の探索2019

    • Author(s)
      古屋欽司 佐古大輔 鄭東旭 岩崎健一 梁宸 古田智章 葛剣云 劉莉萍 打田慶明 八木洋也 濱田洋実 礒田博子 大河内信弘 鄭允文
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A novel rat model of fumarylacetoacetate hydrolase deficient rats with severe combined immunodeficiency2019

    • Author(s)
      葛剣云 張魯狄 古屋欽司 佐古大輔 鄭東旭 梁宸 礒田博子 大河内信弘 惠利健 鄭允文
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Transcriptomics of Patient iPSC-derived Melanocyte Reveals Promising Target Genes of Melanocyte Loss2019

    • Author(s)
      鄭東旭 劉莉萍 李遇梅 鄭允文
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Modeling hepatitis B virus-host interactions in hiPSC derived liver organoids2019

    • Author(s)
      聶 運中 鄭允文 宮川敬 梁明秀 谷口英樹
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 幹細胞からオルガノイドへと肝再生の道2019

    • Author(s)
      鄭允文 佐古大輔 古屋欽司 聶運中 八木洋也 濱田洋実 秋本和憲 礒田博子 谷口英樹 大河内信弘
    • Organizer
      第10回生体表面研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A triple knockout rat model with liver damage and severe combined immunodeficiency2019

    • Author(s)
      葛剣云 鄭允文
    • Organizer
      第30回日本肝臓医生物学研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] RESCUE OF MOUSE ACUTE LIVER FAILURE BY HUMAN LIVER ORGANOIDS GENERATED WITH SINGLE DONOR DERIVED MULTIPLE CELLS.2018

    • Author(s)
      Nie YZ, Zheng YW, Ogawa M, Kurasawa K, Hirahara F, Miyagi E, Taniguchi H.
    • Organizer
      International Society for Stem Cell Research (ISSCR)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] 肝臓外科動態手術教程[紙版&電子版]2020

    • Author(s)
      大河内信弘他(著),鄭允文他(訳)
    • Total Pages
      52
    • Publisher
      中国協和医科大学出版社(北京)
    • ISBN
      9787567914483
    • Related Report
      2020 Annual Research Report
  • [Book] Stem Cells and Cancer in Hepatology: From Essentials to Application.2018

    • Author(s)
      Zheng YW.
    • Total Pages
      382
    • Publisher
      ELSEVIER
    • ISBN
      9780128123010
    • Related Report
      2018 Annual Research Report
  • [Funded Workshop] Annual Meeting of International Society for Stem Cell Research (ISSCR) 20182018

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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