2021 Fiscal Year Final Research Report
Mechanism of chondorogenic differentiation from aged mesencymal stem cells by overexpression of delta133p53
| Project/Area Number |
18H02925
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Akita University (2020-2021)
Kyoto University (2018-2019) |
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Principal Investigator |
Fujita Kaori 秋田大学, 理工学研究科, 講師 (10633092)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Keywords | Δ133p53 / p53 isoform / aging / mesencymal stem cells / differentiation / chondrocytes |
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| Outline of Final Research Achievements |
For therapeutic applications against defects of adult articular cartilage increase with aging, development of regenerative medicine and cartilage tissue engineering are important. However, autologous bone marrow mesenchymal stromal cell (MSC) implantation for elderly individuals is more difficult than young individuals, because capability of cell proliferation and differentiation of the cells decreases in elderly individuals. Cellular senescence contributes to organismal aging and age-related diseases. The p53 signaling network plays a critical role in the induction of cellular senescence. The human TP53 gene encodes twelve natural isoforms. Overexpressing Δ133p53, an anti-senescence p53 isoform, in near-senescent hMSCs and their differentiated chondrocytes showed characteristic differential expression genes in RNA-sequencing. We also obtained many Δ133p53-transcriptional target genes during the chondrogenic differentiation from Δ133p53-overexpressing hMSCs, by Cut & Run-sequencing.
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| Free Research Field |
分子細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
変形性関節症をはじめとする軟骨の加齢性疾患に対する根本的な治療は現在はない。軟骨には血管も神経も通っておらず、自然治癒も期待できない。変形性関節症の罹患率の高い高齢患者からの間葉系幹細胞を用いた再生医療を考える場合、高齢患者の細胞は老化しており、軟骨細胞に分化誘導させることは若年の患者の細胞に比べて非常に困難である。一方、自分の細胞を用いるという点では、拒絶反応の問題がクリアできる。以上より、既に見出した抗老化作用を持つΔ133p53を用いて老化間葉系幹細胞を若返らせ、軟骨細胞に分化誘導する詳細な分子機序を解明するために上記研究を行った。さらに詳細な解析により、誘導法の確立を目指す。
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