2018 Fiscal Year Final Research Report
Regeneration and functional control of the uterus using decellularization technologies in non-human primates
| Project/Area Number |
17K19731
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Surgery related to the biological and sensory functions and related fields
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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) |
升田 博隆 慶應義塾大学, 医学部(信濃町), 講師 (80317198)
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| Research Collaborator |
TAKAO Tomoka
MIYAZAKI Kaoru
MIKI Fumie
YOSHIMASA Yushi
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Keywords | 子宮 / 再生 / 生殖医療 / 組織工学 / iPS細胞 / 脱細胞化 / 再細胞化 |
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| Outline of Final Research Achievements |
For clinical application of uterine bioengineering to patients with partial uterine defects, we selected the Research Center for Animal Life Science, Shiga University of Medical Research, as the place for primate experiments and prepared staff members and experimental setup. To obtain more solid data towards clinical application, we simultaneously performed rat experiments and found that placement of a decellularized uterine scaffold (DUS) led to the regeneration of endometrium with delineated glandular and luminal structures in rat endometrium defect models. The regeneration efficiency, however, was not as high as expected, so we decided to employ DUS loaded with uterine cells to enhance endometrial regeneration. As one of the most likely candidates as the loading cells, we generated progesterone-responsive endometrial stromal from human induced pluripotent stem cells and showed that WNT/CTNNB1 pathway plays a critical role in the differentiation and generation processes.
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| Free Research Field |
産婦人科学
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| Academic Significance and Societal Importance of the Research Achievements |
子宮の先天的・後天的な欠損に対して究極の医療は代理懐胎あるいは子宮移植となるが、安全性や倫理的・法的な問題のため、その実現は極めて難しい。また、これらを部分的な子宮欠損に行うことは過剰な対応である。本研究の成果により部分的な子宮の再生が可能になれば上記の問題は解決され、構造あるいは機能不全を呈する様々な子宮疾患に対して新しい医療になり得る点で、社会的意義は高い。さらに本研究は、世界に先駆けてiPS細胞から子宮構成細胞を作成した点、その過程にWNT/CTNNB1経路が重要な役割を果たしていることなど子宮の発生や分化の生理・病理メカニズムの一端を解明した点で、学術的意義も極めて大きい。
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