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Generation of human iPSCs-derived human salivary gland organoids for orthotopic transplantation

Research Project

Project/Area Number 19H03838
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57040:Regenerative dentistry and dental engineering-related
Research InstitutionShowa University

Principal Investigator

Tanaka Junichi  昭和大学, 歯学部, 講師 (40710166)

Co-Investigator(Kenkyū-buntansha) 安原 理佳  昭和大学, 歯学部, 講師 (20453649)
大庭 伸介  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (20466733)
美島 健二  昭和大学, 歯学部, 教授 (50275343)
辻 孝  国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (50339131)
馬渕 洋  東京医科歯科大学, 大学院医歯学総合研究科, 助教 (50424172)
行森 茜  昭和大学, 歯学部, 助教 (60813748)
桐田 忠昭  奈良県立医科大学, 医学部, 教授 (70201465)
鯨岡 聡子  昭和大学, 歯学部, 助教 (90824673)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2021: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords唾液腺 / オルガノイド / 移植 / iPS細胞 / 同所移植 / 分化誘導 / ヒトiPS細胞
Outline of Research at the Start

本研究では、独自に開発したマウスES細胞由来 唾液腺の分化誘導技術を改変し、ヒトiPS細胞よりヒト唾液腺オルガノイドの誘導、および同所移植による臓器の代替の実現を目的とする。移植可能なヒト唾液腺オルガノイドの作出により、唾液腺障害に対する再生医療への応用や、今まで困難であった唾液腺の病態解析において極めて有用なツールとなることが予想される。

Outline of Final Research Achievements

We have succeeded in inducing salivary gland organoids from human iPS cells by modifying the induction method of salivary gland organoids derived from mouse ES cells. The induced salivary gland organoids were found to have histologically similar morphology to embryonic salivary glands. The scRNA-seq results showed that the salivary gland organoids contained ductal cells, acinar cells, and myoepithelial cells, which are the constituent cells of the salivary gland.
Orthotopic transplantation of these salivary gland organoids into immunodeficient mice with excised parotid glands showed that they functioned in relation to the surrounding tissues.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、移植可能なヒトiPS細胞由来の唾液腺オルガノイドの誘導方法を開発したことでこれまで主にマウスで行ってきた唾液腺発生研究や疾患メカニズムの解析をヒト細胞で行うことが可能となる。また本研究で唾液腺オルガノイドの同所移植によって機能的な唾液腺を再生できる可能性が示され、将来的には唾液腺移植治療への応用が期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (17 results)

All 2022 2021 2020 2019

All Journal Article (9 results) (of which Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Journal Article] Induction of salivary gland-like cells from epithelial tissues transdifferentiated from mouse embryonic fibroblasts2022

    • Author(s)
      Katada Ryogo、Tanaka Junichi、Takamatsu Koki、Hata Kenji、Yasuhara Rika、Ohnuma Shintaro、Takakura Ikuko、Nishimura Riko、Shirota Tatsuo、Mishima Kenji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 586 Pages: 55-62

    • DOI

      10.1016/j.bbrc.2021.11.064

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aging-associated stem/progenitor cell dysfunction in the salivary glands of mice2021

    • Author(s)
      Takamatsu Koki、Tanaka Junichi、Katada Ryogo、Azuma Kotaro、Takakura Ikuko、Aota Keiko、Kamatani Takaaki、Shirota Tatsuo、Inoue Satoshi、Mishima Kenji
    • Journal Title

      Experimental Cell Research

      Volume: 409 Issue: 1 Pages: 112889-112889

    • DOI

      10.1016/j.yexcr.2021.112889

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure of junctional epithelium is maintained by cell populations supplied from multiple stem cells2021

    • Author(s)
      Tanaka Keisuke、Tanaka Junichi、Aizawa Ryo、Kato-Tanaka Mayu、Ueno Hiroo、Mishima Kenji、Yamamoto Matsuo
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 18860-18860

    • DOI

      10.1038/s41598-021-98398-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exploring the mechanism of hyperpermeability following glycocalyx degradation: Beyond the glycocalyx as a structural barrier2021

    • Author(s)
      Abe Kyoko、Tanaka Junichi、Mishima Kenji、Iijima Takehiko
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 6 Pages: e0252416-e0252416

    • DOI

      10.1371/journal.pone.0252416

    • Related Report
      2021 Annual Research Report
    • Open Access
  • [Journal Article] Cdc42 has important roles in postnatal angiogenesis and vasculature formation2021

    • Author(s)
      Yoshida Yuko、Yamada Atsushi、Akimoto Yoshihiro、Abe Kyoko、Matsubara Sachie、Hayakawa Junri、Tanaka Junichi、Kinoshita Mitsuhiro、Kato Tadashi、Ogata Hiroaki、Sakashita Akiko、Mishima Kenji、Kubota Yoshiaki、Kawakami Hayato、Kamijo Ryutaro、Iijima Takehiko
    • Journal Title

      Developmental Biology

      Volume: 477 Pages: 64-69

    • DOI

      10.1016/j.ydbio.2021.05.002

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of regenerative medicine to salivary gland hypofunction2021

    • Author(s)
      Tanaka Junichi、Mishima Kenji
    • Journal Title

      Japanese Dental Science Review

      Volume: 57 Pages: 54-59

    • DOI

      10.1016/j.jdsr.2021.03.002

    • NAID

      210000172902

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sox9 function in salivary gland development.2021

    • Author(s)
      Tanaka J, Takamatsu K, Yukimori A, Kujiraoka S, Ishida S, Takakura I, Yasuhara R, Mishima K.
    • Journal Title

      J Oral Biosci.

      Volume: 63(1) Issue: 1 Pages: 8-13

    • DOI

      10.1016/j.job.2021.01.005

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro three‐dimensional culture systems of salivary glands2020

    • Author(s)
      Tanaka Junichi、Mishima Kenji
    • Journal Title

      Pathology International

      Volume: 70 Issue: 8 Pages: 493-501

    • DOI

      10.1111/pin.12947

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sox9 regulates the luminal stem/progenitor cell properties of salivary glands2019

    • Author(s)
      Tanaka Junichi、Mabuchi Yo、Hata Kenji、Yasuhara Rika、Takamatsu Koki、Kujiraoka Satoko、Yukimori Akane、Takakura Ikuko、Sumimoto Hidetoshi、Fukada Toshiyuki、Azuma Masayuki、Akiyama Haruhiko、Nishimura Riko、Shimane Toshikazu、Mishima Kenji
    • Journal Title

      Experimental Cell Research

      Volume: 382 Issue: 1 Pages: 111449-111449

    • DOI

      10.1016/j.yexcr.2019.05.030

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 多能性幹細胞由来唾液腺オルガノイドの誘導とその応用可能性2021

    • Author(s)
      田中準一
    • Organizer
      日本臨床口腔病理学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 学会奨励賞受賞講演 (Generation of orthotopically functional salivary gland from embryonic stem cell)2021

    • Author(s)
      田中準一
    • Organizer
      日本臨床口腔病理学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 多細胞系譜追跡法を用いたマウス唾液腺細胞系譜の解析2020

    • Author(s)
      田中準一、高松弘貴、行森茜、鯨岡聡子、石田尚子、安原理佳、美島健二
    • Organizer
      第31回日本臨床口腔病理学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The role of FGFs in mouse embryonic stem cells-derived salivary gland organoid culture system2020

    • Author(s)
      田中準一、小川美帆、安原理佳、行森茜、鯨岡聡子、高松弘貴、辻孝、美島健二
    • Organizer
      第109回日本病理学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Generation of functional salivary gland organoid from mouse embryonic stem cells by Sox9 and Foxc1 transduction2019

    • Author(s)
      Tanaka J, Ogawa M, Hojo H, Mabuchi Y, Yasuhara R, Takamatsu K, Ohba S, Tsuji T, Mishima K
    • Organizer
      International Society for Stem Cell Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 唾液腺発生におけるSox9の転写制御ネットワーク機構2019

    • Author(s)
      田中準一, 北條宏徳, 安原理佳, 鯨岡聡子, 行森茜, 大庭伸介, 美島健二
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 唾液腺の基礎研究から再生医療へ2019

    • Author(s)
      田中準一
    • Organizer
      第61回歯科基礎医学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ライフサイエンス研究を支える理研バイオリソース研究センター2019

    • Author(s)
      Tanaka J
    • Organizer
      TSUKUBA CONFERENCE
    • Related Report
      2019 Annual Research Report
    • Invited

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Published: 2019-04-18   Modified: 2023-01-30  

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