| Project/Area Number |
19F19363
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Single-year Grants |
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| Section | 外国 |
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| Review Section |
Basic Section 90110:Biomedical engineering-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
酒井 康行 東京大学, 大学院工学系研究科(工学部), 教授 (00235128)
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| Co-Investigator(Kenkyū-buntansha) |
VADIVELU RAJA 東京大学, 工学(系)研究科(研究院), 外国人特別研究員
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| Project Period (FY) |
2019-11-08 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2021: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2020: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2019: ¥500,000 (Direct Cost: ¥500,000)
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| Keywords | オルガノイド / バイオマテリアル / 発生 / 自己組織化 / 前駆細胞 / 腎臓 / 幹細胞 |
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| Outline of Research at the Start |
腎臓は、２０種類以上の細胞からなる複雑な構造を持つ組織である。しかし発生過程に着目すると、ネフロン、尿管芽、ストローマのわずか３種類の前駆細胞に血管内皮細胞を加えたシンプルな構造から始まり、相互に増殖と分化を制御しながら３次元的に組織化する。これを一部再現するミニチュア腎臓は、創薬毒性試験や疾患モデル、さらには移植用組織として期待されているが、現状では尿排泄経路と血管網が未整備で、局所的かつ不完全な腎構造の再現に止まる。本研究は、工学的・生物学的な知見とアプローチの融合により、３種類の腎前駆細胞の自己組織化を制御することで、尿排泄経路と血管網を備えた移植可能なミニチュア腎臓の構築を目指す。
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| Outline of Annual Research Achievements |
The study of early development during embryogenesis is crucial for advancing fundamental biological and clinical importance. Yet it is limited due to ethical boundaries and the inaccessibility of implanted embryos in utero. Hence, there is a rising demand for developing a synthetic embryonic model called gastruloids by using pluripotent stem cells. The three-dimensional (3D) gastruloids enable the recapitulation of some essential aspects of gastrula-stage embryos including post gastrulation break symmetry and polarized along an anteroposterior axis. However, gastruloid model lacks extraembryonic tissue (EXT) and is imperfect to capture early neural organogenesis. Thus, we aim to improve gastruloid culture
by interfacing human-induced pluripotent stem cells (hiPSCs) with hydrogel-based cryogel. The stiffness of cyrogel can promote cellular response, as softer cryogel (0.5% agarose) showed significant promise to facilitate hiPSCs differentiation on to 3D physiologically relevant organoid model of embryogenesis. These constructs display spatiotemporally confined patterning of neuromesodermal progenitors throughout body axis elongation. We found antagonistic activities of Sox2 and T-bra suggest the specification of neural and mesodermal fates. Collectively, this study may envision that the neuromesodermal patterning define the existence of two distinct routes that contribute to the somites and neural tube.
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| Research Progress Status |
令和3年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
令和3年度が最終年度であるため、記入しない。
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