| Project/Area Number |
18H02866
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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 | University of Tsukuba |
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Principal Investigator |
Zheng Yun-Wen 筑波大学, 医学医療系, 客員研究員 (80404995)
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| Co-Investigator(Kenkyū-buntansha) |
大河内 信弘 筑波大学, 医学医療系, 客員教授 (40213673)
高井 まどか 東京大学, 大学院工学系研究科(工学部), 教授 (40287975)
高橋 一広 筑波大学, 医学医療系, 講師 (80794528)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Keywords | オルガノイド / 肝不全 / 再生医療 / 細胞移植 / ヒト体性幹細胞 / 免疫不全ラット / ヒト化肝臓 / ヒト化ラット / ヒト多能性幹細胞 |
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| Outline of Final Research Achievements |
In this study, we developed an original technology to create novel digestive organoids by using a novel three-dimensional multicellular co-culture system for human placental tissue stem cells and human pluripotent stem cells to mimic the organogenesis process and cell-society interactions in vivo. Furthermore, by transplanting human hepatocytes into immunodeficient rats, it is confirmed human albumin secretion and human-type drug metabolism. We also confirmed the role of macrophages in human-rat xeno-rejection. By expressing the "don't eat me" gene, which induces immune tolerance to human cells, in rats, we can create a new transplantation model that is neither cell transplantation nor organ transplantation, and is expected to make a significant contribution to transplantation medicine and regenerative medicine in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫不全動物を用いて、異種移植におけるマクロファージの種差認識と拒絶に関わる役割の深く理解できたことは、器官移植医療における器官源の作成や移植効率向上に向けた基盤的技術につながると考えられる。また、肝オルガノイドの作成と移植は、消化器系の難治性疾患であり年間死者数が2万人に及ぶ末期肝不全に対する新規治療法となるものである。さらに、この移植・再生医療の新規基盤は、他臓器のオルガノイド移植、ヒト化動物モデルの作成、創薬などの、一連の新しい治療のフロンティアとなりうるものである。
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