2023 Fiscal Year Final Research Report
Functional evaluation of Mullerian duct-like cells derived from mouse embryonic stem cells and elucidation of the uterine regeneration mechanism
| Project/Area Number |
20K18188
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | Mie University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 多能性幹細胞 / ミュラー管様上皮細胞 / 分化誘導 / BMP経路阻害 / FGF 経路活性化 / レチノイン酸経路活性化 |
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| Outline of Final Research Achievements |
Therapies for endometrial dysfunction have shown little improvement, and we are attempting to develop an induction system for Mullerian duct-like epithelial cells (MDECs) with the aim of developing novel therapies. In our previous study, we showed that induction of MDECs requires inhibition of the BMP pathway and activation of the FGF and retinoic acid pathways, but the differentiation efficiency is low. In this study, we confirmed a high differentiation rate of MDECs by differentiation factor X and prolongation of the differentiation period, and subrenal capsulear transplantation of the differentiated cells confirmed endometrial-like glandular luminal structures and localization of endometrial cell marker proteins. Transplantation into a mouse model of endometrial thinning did not show regeneration of endometrial structures, but we plan to optimize the conditions.
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| Free Research Field |
生殖内分泌学
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| Academic Significance and Societal Importance of the Research Achievements |
以前の研究において、ミュラー管様上皮細胞(MDECs)への誘導にはBMP経路の阻害、FGF経路とレチノイン酸経路の活性化が重要である事を示していたが、さらなる高率な誘導のためには、誘導期間の延長と誘導因子Xとの添加が重要であることを実証した。また、誘導した細胞を腎被膜下に移植することで、子宮内膜様構造が形成されることも確認した。
これらの発見は、機序解明のための重要な知見となり学術的意義は大きいと考えられる。また不妊治療において、これまであまり改善していない妊娠率を向上させるための研究ツールを提供するだけでなく、移植細胞療法や再生医療などへの応用も期待でき社会的な意義も大きいと考えられる。
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