Project/Area Number |
21K12686
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 90120:Biomaterials-related
|
Research Institution | Kyushu University |
Principal Investigator |
|
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)
|
Keywords | MSC 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.
|