| Project/Area Number |
16H05474
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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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| Research Field |
Obstetrics and gynecology
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| Research Institution | Keio University |
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Principal Investigator |
MARUYAMA Tetsuo 慶應義塾大学, 医学部(信濃町), 准教授 (10209702)
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| Co-Investigator(Kenkyū-buntansha) |
内田 浩 慶應義塾大学, 医学部(信濃町), 講師 (90286534)
升田 博隆 慶應義塾大学, 医学部(信濃町), 講師 (80317198)
小野 政徳 慶應義塾大学, 医学部(信濃町), 共同研究員 (70348712)
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| Research Collaborator |
TAKAO Tomoka
MIYAZAKI Kaoru
MIKI Fumie
YOSHIMASA Yushi
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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 |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Keywords | 子宮内膜 / 脱細胞化 / 再細胞化 / CRISPR/CAS9 / ゲノム編集 / 再生医療 / 生殖医療 / 光遺伝学 / 子宮再生 / iPS細胞 / 生殖医学 / 細胞治療 / ティッシュエンジニアリング / CRSPR/CAS9 / 幹細胞 / 遺伝子制御 |
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| Outline of Final Research Achievements |
We developed uterine endometrial regeneration technology using decellularized endometrial scaffolds (DES) and photoactivatable CRISPR/CAS9 (paCAS9)-mediated gene editing system to regulate reproductive function in rodents. We showed that placement of DES resulted in the regeneration of endometrium with delineated gland and luminal structures in rat endometrium injury and defect models. Notably, the orientation of the uterine scaffold was important for determination of the tissue topology and architecture of the regenerated uterus. We also found that, in addition to the in vitro gene regulation by paCAS9-mediated gene editing, paCAS was able to regulate uterine gene expression and reproductive functions including uterine embryo receptivity in vivo in response to LED light irradiation. The results of this study provide basic knowledge and technologies to develop a novel therapeutic concept and strategy for restoration and repair of endometrial dysfunction, injury, and defect in humans.
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| Academic Significance and Societal Importance of the Research Achievements |
DESと再細胞化技術による子宮内膜組織の再生は、アッシャーマン症候などの内膜菲薄化・欠損患者に対して有用な治療になり得る。一方、反復着床不全による不妊症や不育症の原因となる内膜の機能不全は、光CAS9という時空間的制御可能なゲノム編集システムを用いて遺伝的アプローチからその異常を是正することにより、改善・解決が可能である。本研究の成果は、新しい内膜機能・構造の再生・再建医療の開発につながる点で社会的意義が大きい。さらに、これらの技術を単独あるいは融合させることにより、子宮内膜の機能と構造を担う分子細胞生物学的メカニズムを明らかにする研究手法ツールになり得る点で、学術的意義も高い。
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