| Project/Area Number |
20K21597
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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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| Review Section |
Medium-sized Section 53:Organ-based internal medicine and related fields
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Okamoto Ryuichi 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50451935)
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| Project Period (FY) |
2020-07-30 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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| Keywords | iPS細胞 / 原腸由来臓器 / スフェロイド / 原腸 / 胚体内胚葉 / 腸 / スフェロイド・デザイニング / 前腸スフェロイド |
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| Outline of Research at the Start |
ヒトiPS細胞より任意デザインの原腸由来臓器を作成するための基盤技術を確立するため、以下３つの課題を計画期間2年で実施する
1) iPS細胞由来前腸スフェロイドの高効率作成法の開発
2) iPS細胞由来前腸スフェロイドの融合・分化能の解析
3)生体内移植による前腸スフェロイド由来臓器の特異的機能獲得の検証
これらで得られた結果に応じ、各臓器の欠損モデルに対する同所移植も試みる事により、特異的機能獲得の有無について検証を行う。
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| Outline of Final Research Achievements |
Through our development of a highly efficient iPS cell-derived primitive-gut spheroid production and the analysis of their fusion/differentiation potential, we have optimized the spheroid-forming method. Also, we have succeeded in developing a method to produce a highly uniform and abundant number of primitive-gut spheroids under the control of their final size and regulate the differentiation of those spheroids. In addition, we have confirmed that those or spheroids can engraft within a certain period after transplantation to severely immunodeficient mice, and also acquire tissue-specific functions and increase their tissue size in vivo. From these results, we have succeeded in developing methods and essential knowledge to induce differentiation from human iPS cells to primitive-gut-derived tissue via the definitive endoderm with the help of both in vitro and in vivo experimental environments.
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| Academic Significance and Societal Importance of the Research Achievements |
高い効率で任意のサイズを有する原腸スフェロイドを作成可能であるばかりでなく、同法で作成したスフェロイドが極めて高い融合指向性と体外環境における原腸由来臓器への分化能を兼ね備えていることを利用し、任意の形状・サイズを有する原腸由来前駆体から原腸由来組織を分化誘導する「スフェロイド・デザイニング」を可能とするための基盤となる知見が確立された。
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