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Induction of tissue-specific stem cells by novel transcription factors and/or small-molecule compounds

Research Project

Project/Area Number 21K19537
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionUniversity of the Ryukyus

Principal Investigator

Noguchi Hirofumi  琉球大学, 医学(系)研究科(研究院), 教授 (50378733)

Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsiTP細胞 / YAP / 転写因子 / 低分子化合物 / iTS細胞 / 膵幹細胞
Outline of Research at the Start

ES/iPS細胞の臨床応用化が進んでいるが、いまだ分化誘導効率の低い臓器・組織が多く存在する。我々のグループは、山中因子を用いて人工組織特異的幹細胞(iTS細胞)の作製に成功している。この細胞は分化誘導効率がES/iPS細胞より高いなどの利点があるが、iTS細胞の樹立にはiPS細胞作製技術を用いているため、作製時にiPS細胞の混入の可能性がある。本研究では、「山中因子以外」の因子を用いてiTS細胞を樹立することを目的としている。具体的には、(1)YAP遺伝子によるiTS細胞の樹立、(2)新規遺伝子によるiTS細胞の樹立、(3) 低分子化合物によるiTS細胞の樹立を試みる。

Outline of Final Research Achievements

Clinical applications of ES/iPS cells are advancing, but there are still many issues that differentiation efficiency of ES/iPS cells is low. Our group has succeeded in induced tissue-specific stem cells (iTS cells) using the Yamanaka factors. These cells have advantages such as higher differentiation efficiency compared to ES/iPS cells, but there is a possibility of iPS cell contamination during iTS cell production because iTS cells are generated by Yamanaka factors. This study aimed to establish iTS cells without the Yamanaka factors. As a result, (1) YAP gene, (2) three novel genes induce iTS cells, but (3) low molecular weight compounds did not induce iTS cells.

Academic Significance and Societal Importance of the Research Achievements

本研究では、「山中因子以外」の因子を用いてiTS細胞を樹立すること成功した。具体的には、(1)YAP遺伝子、(2)新規3遺伝子によるiTS細胞の樹立は可能であった。この2つの樹立方法では、山中因子を使用しないため、iPS細胞の混入の可能性がない。そのため、iPS細胞由来分化細胞の移植の時に問題となる、奇形腫形成を回避することができるため、有用な樹立方法であると考えられる。iTS細胞の特徴として、(a)樹立効率が高い、(b)分化誘導効率が高い、(c)奇形腫形成がない、があるが、今回の研究成果により、さらに安全性が高いiTS細胞の樹立が可能となった。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (18 results)

All 2023 2022 2021 2020

All Journal Article (17 results) (of which Peer Reviewed: 17 results,  Open Access: 17 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Cytoprotective Effect of Pteryxin on Insulinoma MIN6 Cells Due to Antioxidant Enzymes Expression via Nrf2/ARE Activation2023

    • Author(s)
      Taira Junsei、Tsuda Ryuji、Miyagi-Shiohira Chika、Noguchi Hirofumi、Ogi Takayuki
    • Journal Title

      Antioxidants

      Volume: 12 Issue: 3 Pages: 693-693

    • DOI

      10.3390/antiox12030693

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Islet Transplantation Covered by Health Insurance in Japan2022

    • Author(s)
      Noguchi Hirofumi
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Issue: 14 Pages: 3977-3977

    • DOI

      10.3390/jcm11143977

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pancreas Preservation with a Neutrophil Elastase Inhibitor, Alvelestat, Contributes to Improvement of Porcine Islet Isolation and Transplantation.2022

    • Author(s)
      Ryusei Otsuka, Chika Miyagi-Shiohira, Kazuho Kuwae, Kai Nishime, Yoshihito Tamaki, Tasuku Yonaha, Mayuko Sakai-Yonaha, Ikuo Yamasaki, Misaki Shinzato, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi
    • Journal Title

      Journal of clinical medicine

      Volume: 11.15 Issue: 15 Pages: 4290-4290

    • DOI

      10.3390/jcm11154290

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] AP39, a Mitochondrial-Targeted H2S Donor, Improves Porcine Islet Survival in Culture.2022

    • Author(s)
      Misaki Shinzato , Chika Miyagi-Shiohira , Kazuho Kuwae , Kai Nishime , Yoshihito Tamaki , Tasuku Yonaha , Mayuko Sakai-Yonaha , Ikuo Yamasaki , Ryusei Otsuka , Issei Saitoh , Masami Watanabe , Hirofumi Noguchi
    • Journal Title

      Journal of clinical medicine

      Volume: 11.18 Issue: 18 Pages: 5385-5385

    • DOI

      10.3390/jcm11185385

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induced hepatic stem cells are suitable for human hepatocyte production2022

    • Author(s)
      Nakashima Yoshiki、Miyagi-Shiohira Chika、Saitoh Issei、Watanabe Masami、Matsushita Masayuki、Tsukahara Masayoshi、Noguchi Hirofumi
    • Journal Title

      iScience

      Volume: 25 Issue: 10 Pages: 105052-105052

    • DOI

      10.1016/j.isci.2022.105052

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of Genetically Modified Human Feeder Cells in Maintaining the Integrity of Primary Cultured Human Deciduous Dental Pulp Cells.2022

    • Author(s)
      Ibano N、Inada E、Otake S、Kiyokawa Y、Sakata K、Sato M、Kubota N、Noguchi H、Iwase Y、Murakami T、Sawami T、Kakihara Y、Maeda T、Terunuma M、Terao Y、Saitoh I
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Issue: 20 Pages: 6087-6087

    • DOI

      10.3390/jcm11206087

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Evaluation of 3D Liver Models Labeled with Polysaccharide Functionalized Magnetic Nanoparticles2022

    • Author(s)
      Miyamoto Yoshitaka、Koshidaka Yumie、Murase Katsutoshi、Kanno Shoichiro、Noguchi Hirofumi、Miyado Kenji、Ikeya Takeshi、Suzuki Satoshi、Yagi Tohru、Teramoto Naozumi、Hayashi Shuji
    • Journal Title

      Materials

      Volume: 15 Issue: 21 Pages: 7823-7823

    • DOI

      10.3390/ma15217823

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protocol for the generation of human induced hepatic stem cells using Sendai virus vectors2022

    • Author(s)
      Noguchi Hirofumi、Nakashima Yoshiki、Watanabe Masami、Matsushita Masayuki、Tsukahara Masayoshi、Saitoh Issei、Miyagi-Shiohira Chika
    • Journal Title

      STAR Protocols

      Volume: 3 Issue: 4 Pages: 101884-101884

    • DOI

      10.1016/j.xpro.2022.101884

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pancreas Preservation in Modified Histidine-lactobionate Solution Is Superior to That in University of Wisconsin Solution for Porcine Islet Isolation2021

    • Author(s)
      Sakai-Yonaha Mayuko、Miyagi-Shiohira Chika、Kuwae Kazuho、Tamaki Yoshihito、Nishime Kai、Yonaha Tasuku、Saitoh Issei、Watanabe Masami、Noguchi Hirofumi
    • Journal Title

      Transplantation

      Volume: Publish Ahead of Print Issue: 9 Pages: 1770-1776

    • DOI

      10.1097/tp.0000000000003636

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene Expression in Pancreatic Cancer-Like Cells and Induced Pancreatic Stem Cells Generated by Transient Overexpression of Reprogramming Factors2021

    • Author(s)
      Miyagi-Shiohira Chika、Saitoh Issei、Watanabe Masami、Noguchi Hirofumi
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 3 Pages: 454-454

    • DOI

      10.3390/jcm10030454

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] RNA analysis based on a small number of manually isolated fixed cells (RNA-snMIFxC) to profile stem cells from human deciduous tooth-derived dental pulp cells2021

    • Author(s)
      Inada E, Saitoh I, Kubota N, Iwase Y, Kiyokawa Y, Noguchi H, Yamasaki Y, Sato M
    • Journal Title

      Biological Procedure Online

      Volume: 23 Issue: 1 Pages: 12-12

    • DOI

      10.1186/s12575-021-00149-5

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induced Tissue-Specific Stem Cells (iTSCs): Their Generation and Possible Use in Regenerative Medicine2021

    • Author(s)
      Saitoh Issei、Sato Masahiro、Kiyokawa Yuki、Inada Emi、Iwase Yoko、Ibano Natsumi、Noguchi Hirofumi
    • Journal Title

      Pharmaceutics

      Volume: 13 Issue: 6 Pages: 780-780

    • DOI

      10.3390/pharmaceutics13060780

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pancreas preservation with amphotericin B deteriorates islet yield for porcine islet isolation2021

    • Author(s)
      Sawada Sayaka、Miyagi‐Shiohira Chika、Kuwae Kazuho、Tamaki Yoshihito、Nishime Kai、Sakai‐Yonaha Mayuko、Yonaha Tasuku、Saitoh Issei、Watanabe Masami、Noguchi Hirofumi
    • Journal Title

      Xenotransplantation

      Volume: 28 Issue: 4

    • DOI

      10.1111/xen.12690

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo evaluation ofGG2-GG1/ A2 element activity in the insulin promoter region using the CRISPR-Cas9 system2021

    • Author(s)
      Hirofumi Noguchi Chika Miyagi Shiohira Takao Kinjo Issei Saitoh MasamiWatanabe
    • Journal Title

      Scientifc Reports

      Volume: 11:20290 Issue: 1 Pages: 20290-20290

    • DOI

      10.1038/s41598-021-99808-6

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tissue-nonspecific alkaline phosphatase, a possible mediator of cell maturation: Towards a new paradigm2021

    • Author(s)
      Sato M, Saitoh I, Kiyokawa, Iwase Y, Kubota N, Ibano N, Noguchi H, Yamasaki Y, Inada E
    • Journal Title

      Cells

      Volume: 10 Issue: 12 Pages: 3338-3338

    • DOI

      10.3390/cells10123338

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pancreas preservation in extracellular‐type p38 inhibitor‐containing solution improves islet yield for porcine islet isolation2020

    • Author(s)
      Yonaha Tasuku、Miyagi‐Shiohira Chika、Kuwae Kazuho、Tamaki Yoshihito、Nishime Kai、Sakai‐Yonaha Mayuko、Saitoh Issei、Watanabe Masami、Noguchi Hirofumi
    • Journal Title

      Xenotransplantation

      Volume: 28 Issue: 2

    • DOI

      10.1111/xen.12661

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preservation of pancreas in the University of Wisconsin solution supplemented with AP39 reduces reactive oxygen species production and improves islet graft function2020

    • Author(s)
      Nishime Kai、Miyagi‐Shiohira Chika、Kuwae Kazuho、Tamaki Yoshihito、Yonaha Tasuku、Sakai‐Yonaha Mayuko、Saitoh Issei、Watanabe Masami、Noguchi Hirofumi
    • Journal Title

      American Journal of Transplantation

      Volume: in press Issue: 8 Pages: 2698-2708

    • DOI

      10.1111/ajt.16401

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Patent(Industrial Property Rights)] ヒト膵臓組織特異的幹/前駆細部の人工作製方法2021

    • Inventor(s)
      野口洋文
    • Industrial Property Rights Holder
      国立大学法人琉球大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Acquisition Date
      2023
    • Related Report
      2023 Annual Research Report

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Published: 2021-07-13   Modified: 2025-01-30  

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