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Understanding the effects of substrate stiffness on rejuvenation of aging MSCs via single cell analysis.

Research Project

Project/Area Number 21K12686
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionKyushu University

Principal Investigator

KUBOKI Thasaneeya  九州大学, 先導物質化学研究所, 助教 (20526834)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsMSC aging / cellular senescence / rejuvenation / substrate elasticity / gelatinous hydrogel / redox homeostasis / DNA damage response / single cell analysis / substrate stiffness / cell cycle / mechano-regulation / redox balance
Outline of Research at the Start

The key question for this proposal is how the substrate stiffness could maintain the MSC quality and delay the aging. The central hypothesis is that the compliance substrates could reduce CSKs tension, increase their dynamics and the activate the antioxidant system to maintain the redox homeostasis. Increasing of aging population and aged-related diseases increase the health problems. Identification of key targets for preventing or ameliorating senescence is essential for precisely engineered mechanical substrate to slow or reverse the age-related reduction of MSC properties.

Outline of Final Research Achievements

This study demonstrated the rejuvenation capacity of the gelatinous hydrogels to delay/reverse senescence of the mesenchymal stem cells (MSCs).The hydrogels could increase the proliferation and osteogenic differentiation and enhance the motility of the aged MSCs. Single cell real time PCR analysis results illustrated the activation of signaling molecules in longevity and rejuvenation related pathways such as SIRT, FOXO, AMPK and NAMPT in the MSCs on gels. These results demonstrated that the the hydrogels could better maintain redox homeostasis, reduce cytoskeletal tension, enhance the recovery of actin dynamic and activate the signaling pathways related to longevity and rejuvenation of the MSCs.

Academic Significance and Societal Importance of the Research Achievements

Increasing of aging population and aged-related diseases increase the health problems. Identification of key targets for preventing or ameliorating senescence is essential for precisely engineered mechanical substrate to slow or reverse the age-related reduction of MSC properties.

Report

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

    (6 results)

All 2024 2023 2022

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] A plasmonic metasurface reveals differential motility of breast cancer cell lines at initial phase of adhesion2024

    • Author(s)
      Lee Shi Ting、Kuboki Thasaneeya、Kidoaki Satoru、Aida Yukiko、Arima Yusuke、Tamada Kaoru
    • Journal Title

      Colloids and Surfaces B: Biointerfaces

      Volume: 238 Pages: 113876-113876

    • DOI

      10.1016/j.colsurfb.2024.113876

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Elucidation of substrate stiffness mediated rejuvenation mechanism of aging stem cells through the regulation of cellular homeostasis.2023

    • Author(s)
      Kuboki Thasaneeya
    • Organizer
      The 96th Annual Meeting of Japanese Biochemical Society.
    • Related Report
      2023 Annual Research Report
  • [Presentation] Elucidation of substrate stiffness mediated rejuvenation mechanism of aging stem cells through the mechano-regulation of cellular homeostasis.2023

    • Author(s)
      Kuboki Thasaneeya
    • Organizer
      MBSJ 2023
    • Related Report
      2023 Annual Research Report
  • [Presentation] Understanding the mecahno-regulation of substrate stiffness on rejuvenation mechanism of aging stem cell2022

    • Author(s)
      Kuboki Thasaneeya
    • Organizer
      world congress of biomechanics
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Understanding the mecahno-regulation of substrate stiffness on rejuvenation mechanism of aging stem cell2022

    • Author(s)
      Kuboki Thasaneeya
    • Organizer
      The Japan Society of Mechanical Engineers
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Understanding the mecahno-regulation of substrate stiffness on rejuvenation mechanism of aging stem cell2022

    • Author(s)
      Kuboki Thasaneeya
    • Organizer
      Molecular Biology Society of Japan
    • Related Report
      2022 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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