| Project/Area Number |
16K08234
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo University of Science, Yamaguchi (2018)
Hiroshima University (2016-2017) |
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Principal Investigator |
Shimamoto Akira 山陽小野田市立山口東京理科大学, 薬学部, 教授 (70432713)
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| Research Collaborator |
Yokote Koutaro
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 早老症 / 細胞老化 / 間葉系幹細胞 / ウェルナー症候群 / 多能性幹細胞 / ゲノム編集 / p53遺伝子変異 / 皮膚潰瘍モデル / p21 / p16 / SA-β-gal / 人工多能性幹細胞 / 細胞移植治療 |
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| Outline of Final Research Achievements |
Werner syndrome (WS) is a genetic disorder characterized by early onset of age-related diseases. In this study, we established WS-iPSCs toward elucidation of an effect of reprogramming on premature senescence of WS cells, and elucidation of pathology of WS and therapeutic development for WS. WS-iPSCs acquired undifferentiated state and showed pluripotency as is the case in normal iPSCs. On the other hand, mesenchymal stem cells (MSCs) derived from WS-iPSCs (WS-MSCs) showed upregulation of senescence-associated genes, telomere shortening, enhancement of DNA damage response, when compared with normal MSCs, which is suggesting premature senescence phenotype in WS-MSCs. These basic findings may provide the possibility of a new approach for therapeutic development based on MSCs for WS.
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| Academic Significance and Societal Importance of the Research Achievements |
ウェルナー症候群は種々の加齢疾患を20代より加速的に発症する遺伝的早老症で、症状は全身性で皮膚萎縮・硬化、インスリン耐性糖尿病、骨粗鬆症、動脈硬化、悪性腫瘍など多岐にわたる。病態解明や治療法確立には原因となる細胞種を明らかにすることが必要不可欠であり、本疾患の病態を表現する細胞種をMSCとして同定したことは、学術的にも応用の見地からも大いに意義がある。またウェルナー症候群は世界的には日本での症例報告が圧倒的に多く、老化の病態が間葉系幹細胞の老化であることを明らかにした本研究の社会的意義は非常に大きく、間葉系幹細胞を用いた加齢疾患に対する再生医療の可能性の扉を開くものである。
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