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Cell fate determination of mesenchymal stem cells by extracellular mechanical stress

Research Project

Project/Area Number 17H04414
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthodontics/Pediatric dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

IWAMOTO Tsutomu  徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (90346916)

Co-Investigator(Kenkyū-buntansha) 山本 朗仁  徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (50244083)
長谷川 智一  徳島大学, 大学院医歯薬学研究部(歯学域), 講師 (50274668)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Keywords間葉系幹細胞 / 細胞外圧 / 静水圧 / 細胞分化 / 脱落乳歯歯髄幹細胞 / 細胞外環境 / 加圧培養 / 分化促進 / 骨芽細胞 / 象牙芽細胞 / 唾液腺
Outline of Final Research Achievements

There are many unclear points regarding the mechanism of the fate determination of tissue-derived mesenchymal stem cells (MSCs), which is a candidate as a cell source for regenerative medicine. The interactions of the Cell-cell or cell-extracellular environment would regulate the cell fate determination of MSCs. Because cells are surrounded by extracellular fluid, and it is thought that all of these signals are transmitted into the cell via the extracellular fluid. Therefore, among them, we focused on hydrostatic pressure and analyzed the effect of hydrostatic pressure on the differentiation of bone marrow-derived MSCs and stem cells from human exfoliated deciduous teeth. As the result, hydrostatic pressure promoted differentiation into osteoblasts or odontoblasts. We found that PIEZO1has an important role in cell fate determination through its mechanotransduction.

Academic Significance and Societal Importance of the Research Achievements

再生医療に有効な細胞供給源として,それぞれの組織に存在する多能性を有した間葉系幹細胞の応用法の開発が期待されている。しかし,一般にそれらの幹細胞を再生医療に用いる目的の細胞へと分化誘導する際には,高額なサイトカイン等を用いる必要がある。そこで本研究において,細胞外圧に着目し,細胞外圧の強さを変動させることによって,細胞分化を誘導する方法を見出した。つまり細胞外圧をコントロールすることによって,細胞自身が持つ分化誘導能を賦活化させることが可能となることを明らかにした。このことは細胞分化に高額な費用をかけずに細胞を分化誘導させる手法として,再生医療へ応用できる技術になると考えられた。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report

Research Products

(7 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (3 results)

  • [Journal Article] Coordination of WNT signaling and ciliogenesis during odontogenesis by piezo type mechanosensitive ion channel component 1.2019

    • Author(s)
      Miyazaki A, Sugimoto A, Yoshizaki K, Kawarabayashi K, Iwata K, Kurogoushi R, Kitamura T, Otsuka K, Hasegawa T, Akazawa Y, Fukumoto S, Ishimaru N, Iwamoto T.
    • Journal Title

      Scientific Reports

      Volume: 9(1) Pages: 1-13

    • DOI

      10.1038/s41598-019-51381-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination of ions promotes cell migration via extracellular signal-regulated kinase 1/2 signaling pathway in human gingival fibroblasts.2019

    • Author(s)
      Yamaguchi-Ueda K, Akazawa Y, Kawarabayashi K, Sugimoto A, Nakagawa H, Miyazaki A, Kurogoushi R, Iwata K, Kitamura T, Yamada A, Hasegawa T, Fukumoto S, Iwamoto T.
    • Journal Title

      Molecular Medicine Reports

      Volume: 19(6) Pages: 3406-3418

    • DOI

      10.3892/mmr.2019.10141

    • NAID

      120006731791

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Piezo type mechanosensitive ion channel component 1 functions as a regulator of the cell fate determination of mesenchymal stem cells2017

    • Author(s)
      Sugimoto Asuna, Miyazaki Aya, Kawarabayashi Keita, Masayuki Shono, Yuki Akazawa, Tomokazu Hasegawa, Kimiko Ueda Yamaguchi, Takamasa Kitamura, Yoshizaki keigo, Fukumoto Satoshi and Tsutomu Iwamoto
    • Journal Title

      Sci Rep.

      Volume: 7 Pages: 17696-17696

    • DOI

      10.1038/s41598-017-18089-0

    • NAID

      120006535026

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pannexin 3 regulates proliferation and differentiation of odontoblasts via its hemichannel activities2017

    • Author(s)
      Iwamoto Tsutomu、Nakamura Takashi、Ishikawa Masaki、Yoshizaki Keigo、Sugimoto Asuna、Ida-Yonemochi Hiroko、Ohshima Hayato、Saito Masahiro、Yamada Yoshihiko、Fukumoto Satoshi
    • Journal Title

      PLoS One

      Volume: 12 Pages: 0177557-0177557

    • DOI

      10.1371/journal.pone.0177557

    • NAID

      120006534958

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 静水圧負荷刺激により誘導される象牙質形成機転の解明2019

    • Author(s)
      宮嵜 彩, 杉本 明日菜, 岩本 勉
    • Organizer
      第57回日本小児歯科学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 象牙芽細胞におけるピエゾ型イオンチャネル1(PIEZO1)の発現とその役割2018

    • Author(s)
      杉本 明日菜, 宮嵜 彩, 河原林 啓太, 岩田 こころ, 黒厚子 璃佳, 赤澤 友基, 長谷川 智一, 上田(山口) 公子, 北村 尚正, 中川 弘, 岩本 勉
    • Organizer
      第37回日本小児歯科学会中四国地方会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PIEZO1は歯髄細胞の分化運命決定に関与し,象牙芽細胞への分化を促進させる2017

    • Author(s)
      杉本明日菜,赤澤友基,長谷川智一,宮嵜 彩,河原林啓太,岩本 勉
    • Organizer
      第55回日本小児歯科学会大会
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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