| Project/Area Number |
18H02867
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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 55010:General surgery and pediatric surgery-related
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| Research Institution | Juntendo University (2019-2020)
Tokyo Medical and Dental University (2018) |
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Principal Investigator |
Tetsuya Nakamura 順天堂大学, 医学(系)研究科(研究院), 特任教授 (70265809)
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| Co-Investigator(Kenkyū-buntansha) |
松本 有加 順天堂大学, 医学部, 助教 (50813672)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 腸オルガノイド / 腸上皮幹細胞 / 腸管不全 / 再生医療 / オルガノイド移植 / 腸再生医療 / 小腸移植 / 細胞移植 |
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| Outline of Final Research Achievements |
Extensive resection of the small intestine (SI) leads to severe short bowel syndrome (SBS). To explore a new approach for regenerative medicine for this condition, we have developed in this study a mouse model of local replacement of the colon epithelium with the SI one, by removing the colonic mucosa with chelating agents and subsequently transplanting SI organoids. We found that adult SI organoids regenerate new epithelia that morphologically preserve mature SI phenotypes even in the colonic environment after engraftment. Molecular as well as histological analyses confirmed the preservation of gene and protein expression patterns of SI epithelial cells in the ectopically grafted tissue. The results of our study suggest that the mesenchymal component of the remnant colon in SBS patients would provide a scaffold for the SI organoid transplantation, which may compensate for the loss of function of the SI in SBS patients.
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| Academic Significance and Societal Importance of the Research Achievements |
広汎な小腸切除などで生じる腸管不全に対する新規治療開発が切望されてきた。本研究では、マウス大腸上皮を安全に剥離し、培養オルガノイド移植によりこれを小腸上皮に置換する技術を提示した。また、異所性に移植生着させた小腸上皮移植片は、小腸上皮固有の分子発現パターンを保持することも明らかになった。
本研究成果と今後のさらなる進展により、重篤なヒト腸管不全に対し、既存の大腸組織を足場として利用することにより、血流確保術を必要とせずに広大な小腸粘膜を創出する全く新しい腸再生医療技術を提供できる可能性がある。
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