2023 Fiscal Year Annual Research Report
Understanding the effects of substrate stiffness on rejuvenation of aging MSCs via single cell analysis.
| Project/Area Number |
21K12686
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| Research Institution | Kyushu University |
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Principal Investigator |
久保木 タッサニーヤー 九州大学, 先導物質化学研究所, 助教 (20526834)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | MSC aging / cellular senescence / rejuvenation / substrate elasticity / gelatinous hydrogel / redox homeostasis / substrate stiffness / single cell analysis |
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| Outline of Annual Research Achievements |
This study demonstrated the rejuvenation capacity of the surface elasticity tunable gelatinous hydrogels to delay/reverse senescence phenotypes of the mesenchymal stem cells (MSCs). The hydrogels could rescue the therapeutic properties of the late passages MSCs, as suggested by the reducing the numbers of DNA damage positive cells, increasing the proliferation and osteogenic differentiation potencies, decreasing the nuclear and cell size and increased their motility. Single cell real time PCR analysis was performed to investigate the specific gene expression patterns encoded within RNA of the individual MSCs to gain a better understanding of the substrate stiffness induced MSC rejuvenation in single cell resolution. With the high throughput approach, senescence, antioxidant, cytoprotective, longevity, and rejuvenation related genes could be simultaneously quantified. The results illustrated the activation of several regulators and signaling molecules in longevity and rejuvenation related pathways such as SIRT, FOXO, AMPK and NAMPT in the MSCs maintained on gels.
In summary, the results from this study demonstrated that the MSCs cultured on the hydrogels possessed higher radical scavenging capacity and could better maintain redox homeostasis, reduce CSK tension, enhance the recovery of actin dynamic and activate the signaling pathways related to longevity and rejuvenation.
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