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Maintenance of undifferentiated state and cell fate tracing by visualization of mesenchymal stem cells in vivo

Research Project

Project/Area Number 16H05173
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionShimane University

Principal Investigator

Matsuzaki Yumi  島根大学, 学術研究院医学・看護学系, 教授 (50338183)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords間葉系幹細胞 / 未分化性維持 / Wntシグナル / Notchシグナル / レポーター遺伝子 / 体内動態 / 細胞運命トレーシング / 細胞・組織 / FZD5 / 細胞運命 / 実験動物 / Notch2 / 分子機構
Outline of Final Research Achievements

By systematically elucidating the molecular mechanism in determining the undifferentiated maintenance of MSC and determining the direction of differentiation in this study, the mechanism to control the undifferentiated maintenance of stem cells / progenitor cells / mature cells and the directionality of differentiation is inscribed. An attempt was made to understand both in vivo and in vitro. As a result, FZD5 suppresses cellular senescence by activating the non-classical pathway by forced expression and knockdown of FZD5 and Notch2, and that Notch2 is upregulated under hypoxic conditions and induces cell proliferation It became clear. Furthermore, we generated a reporter transgenic mouse using MSC specific gene expression regulatory region and clarified that its expression is localized to undifferentiated MSC.

Academic Significance and Societal Importance of the Research Achievements

多くのMSC研究は培養MSC又は不死化した細胞株を用いた実験に頼らざるを得ず、得られた結果が真にMSCの性状を反映したものかは不明であった。また、生体内での性状解析もほとんど解析されて来なかった。本研究では、高純度のヒトMSC(REC)を用いて未分化性維持機構の解析を行った。さらに、独自に開発したレポーターマウスを用いて、MSCからの間質細胞への細胞系譜の可視化と動態の解析を行った。これらのアプローチは、個々の細胞が持つ性質を解析する上で生理的条件に最も近く、間葉細胞系譜の生理機能を本質的に理解するには必要かつ適切であり、学術的ばかりでなく、安全な先進医療を確立する上でも大きな意義を持つ。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] Construction of Continuous Capillary Networks Stabilized by Pericyte-like Perivascular Cells2019

    • Author(s)
      Kyoko Yamamoto, Kohei Tanimura, Masafumi Watanabe, Hiromu Sano, Hiroyuki Uwamori, Yo Mabuchi, Yumi Matsuzaki, Seok Chung, Roger D. Kamm, Kazuo Tanishita, Ryo Sudo
    • Journal Title

      Tissue Engineering Part A

      Volume: 25 Issue: 5-6 Pages: 499-510

    • DOI

      10.1089/ten.tea.2018.0186

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bioactive/Bioresorbable Three-Dimensional Porous Uncalcined and Unsintered Hydroxyapatite/Poly-D/L-lactide Composite with Human Mesenchymal Stem Cells for Bone Regeneration in Maxillofacial Surgery: A Pilot Animal Study2019

    • Author(s)
      Jingjing Sha, Takahiro Kanno, Kenichi Miyamoto, Yunpeng Bai, Katsumi Hideshima, Yumi Matsuzaki
    • Journal Title

      Materials

      Volume: 12 Issue: 5 Pages: 705-705

    • DOI

      10.3390/ma12050705

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peptide barcoding for establishment of new types of genotype-phenotype linkages.2019

    • Author(s)
      Miyamoto K, Aoki W, Ohtani Y, Miura N, Aburaya S, Matsuzaki Y, Kajiwara K, Kitagawa Y, Ueda M.
    • Journal Title

      PLoS One

      Volume: 14 Issue: 4 Pages: e0215993-e0215993

    • DOI

      10.1371/journal.pone.0215993

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Feasibility of a three-dimensional porous uncalcined and unsintered hydroxyapatite/poly-D/L-lactide composite for the regenerative biomaterial in maxillofacial surgery2018

    • Author(s)
      Yunpeng Bai, Takahiro Kanno, Hiroto Tatsumi, Kenichi Miyamoto, Jingjing Sha, Katsumi Hideshima, Yumi Matsuzaki
    • Journal Title

      Materials

      Volume: 11 Issue: 10 Pages: 2047-2047

    • DOI

      10.3390/ma11102047

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 成体幹細胞についての最近のトピックス2018

    • Author(s)
      吉川倫太郎, 宮城聡, 松崎有未
    • Journal Title

      日本再生医療学会雑誌

      Volume: 17 Pages: 30-44

    • NAID

      40021890942

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Induction of hair follicle dermal papilla cell properties in human induced pluripotent stem cell-derived multipotent LNGFR(+)THY-1(+) mesenchymal cells.2017

    • Author(s)
      Veraitch O, Mabuchi Y, Matsuzaki Y, Sasaki T, Okuno H, Tsukashima A, Amagai M, Okano H, Ohyama M.
    • Journal Title

      Scientific Reports

      Volume: 7 Pages: 42777-42777

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Isolation of dental pulp stem cells with high osteogenic potential.2017

    • Author(s)
      Yasui T, Mabuchi Y, Morikawa S, Onizawa K, Akazawa C, Nakagawa T, Okano H, Matsuzaki Y.
    • Journal Title

      Inflammation and Regeneration

      Volume: 37 Pages: 1-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] フローサイトメトリーによるマウス間葉系幹細胞分離法2017

    • Author(s)
      松崎有未, 吉川倫太郎, 小松貴義, 宮内裕美, 陶山隆史, 宮本憲一
    • Journal Title

      サイトメトリーリサーチ

      Volume: 27 Pages: 41-45

    • NAID

      130006832439

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 間葉系幹細胞の分類とその臨床応用2017

    • Author(s)
      松崎有未, 宮本憲一
    • Journal Title

      再生医療

      Volume: 16 Pages: 20-25

    • NAID

      40021330371

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Notch2 Signaling Regulates the Proliferation of Murine Bone Marrow-Derived Mesenchymal Stem/Stromal Cells via c-Myc Expression.2016

    • Author(s)
      Sato Y, Mabuchi Y, Miyamoto K, Araki D, Niibe K, Houlihan DD, Morikawa S, Nakagawa T, Nakajima T, Akazawa C, Hori S, Okano H, Matsuzaki Y.
    • Journal Title

      PLoS One.

      Volume: 11

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 超高純度ヒト間葉系幹細胞 "REC" -再生医療に向けて-2018

    • Author(s)
      松崎有未
    • Organizer
      第39回 日本炎症再生学会 教育講演
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 間葉系幹細胞分離とトランスレーションへの挑戦2018

    • Author(s)
      松崎有未
    • Organizer
      第28回 日本フローサイトメトリー学会学術集会 会長講演
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 高純度ヒト間葉系幹細胞”REC”による希少疾患治療展望2018

    • Author(s)
      松崎有未
    • Organizer
      第8回細胞再生医療研究会 シンポジウム1
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Purified human bone marrow derived mesenchymal stem cell “REC”2018

    • Author(s)
      松崎有未
    • Organizer
      中日免疫医学峰会(天津)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 超高純度ヒト間葉系幹細胞 "REC"2017

    • Author(s)
      松崎有未
    • Organizer
      第38回 日本炎症再生学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 超高純度ヒト骨髄由来間葉系幹細胞の分離とその性状解析2017

    • Author(s)
      松崎有未
    • Organizer
      日本放射線影響学会第60回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 超高純度間葉系幹細胞の分離とその臨床応用への展望2017

    • Author(s)
      松崎有未
    • Organizer
      第22回東海HSCT懇話会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Human cell therapy by purified human bone marrow derived stem cells2017

    • Author(s)
      松崎有未
    • Organizer
      Asian cellular therapy organization, ACTO 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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