Modeling monogenic steatohepatitis using human liver organoids
Project/Area Number |
18H02800
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Takebe Takanori 東京医科歯科大学, 統合研究機構, 教授 (20612625)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
|
Keywords | 脂肪性肝炎 / 線維化 / Wolman病 / オルガノイド / レチノイン酸 |
Outline of Final Research Achievements |
In this study we developed a robust method to derive multi-cellular human liver organoids including immune components that exhibit resemblance to in vivo-derived tissues. Under free fatty acid treatment, the organoids recapitulated key features of steatohepatitis in a successive manner. Furthermore, organoids from patients of Wolman disease, which is a congenital steatohepatitis driven by loss-of-function mutation of lysosomal acid lipase, phenocopied severe steatohepatitis.
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Academic Significance and Societal Importance of the Research Achievements |
免疫系細胞(マクロファージ様細胞)が出現するオルガノイド技術を開発したことにより、肺や腸などを含むさまざまな臓器の炎症・線維化疾患に対する研究に、類似の手法が有効となる可能性が考えられる。さらに、従来の動物モデルやオルガノイド技術では困難だった、脂肪性肝炎等の患者数の多い複雑なヒト疾患メカニズムの理解の加速に大きく貢献すると期待される。将来的には、ヒト脂肪性肝炎の患者病態の再現に優れている特徴を活用し、オルガノイドを用いた創薬スクリーニングを通じて、未だ有効な治療薬のない脂肪性肝炎に対する新薬の開発へつながることも期待される。
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Report
(4 results)
Research Products
(96 results)
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[Journal Article] High-Fidelity Drug-Induced Liver Injury Screen Using Human Pluripotent Stem Cell?Derived Organoids2021
Author(s)
Shinozawa T, Kimura M, Cai Y, Saiki N, Yoneyama Y, Ouchi R, Koike H, Maezawa M, Zhang RR, Dunn A, Ferguson A, Togo S, Lewis K, Thompson WL, Asai A, Takebe T.
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Journal Title
Gastroenterology
Volume: 160
Issue: 3
Pages: 831-846.e10
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Simultaneous Zn2+ tracking in multiple organelles using super-resolution morphology-correlated organelle identification in living cells2021
Author(s)
Fang H, Geng S, Hao M, Chen Q, Liu M, Liu C, Tian Z, Wang C, Takebe T, Guan JL, Chen Y, Guo Z, He W, Diao J.
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Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 109-109
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Modeling Human Bile Acid Transport and Synthesis in Stem Cell-Derived Hepatocytes with a Patient-Specific Mutation2021
Author(s)
Hayashi H, Osaka S, Sakabe K, Fukami A, Kishimoto E, Aihara E, Sabu Y, Mizutani A, Kusuhara H, Naritaka N, Zhang W, Huppert SS, Sakabe M, Nakamura T, Hu YC, Mayhew C, Setchell K, Takebe T, Asai A.
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Journal Title
Stem Cell Reports
Volume: 16
Issue: 2
Pages: 309-323
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection2021
Author(s)
Dobrindt K, Hoagland DA, Seah C, Kassim B, OShea CP, Murphy A, Iskhakova M, Fernando MB, Powell SK, Deans PJM, Javidfar B, Peter C, Muller R, Uhl SA, Garcia MF, Kimura M, Iwasawa K, Crary JF, Kotton DN, Takebe T, Huckins LM, tenOever BR, Akbarian S, Brennand KJ.
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Journal Title
Stem Cell Reports
Volume: 16
Issue: 3
Pages: 505-518
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Voices of biotech research2021
Author(s)
Annabi N, ..., Takebe T, Vandenberghe LH, Varshney RK, Wang J.
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Journal Title
Nature Biotechnology
Volume: 39
Issue: 3
Pages: 281-286
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis.2020
Author(s)
Han L, Chaturvedi P, Kishimoto K, Koike H, Nasr T, Iwasawa K, Giesbrecht K, Witcher PC, Eicher A, Haines L, Lee Y, Shannon JM, Morimoto M, Wells JM, Takebe T, Zorn AM.
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Journal Title
Nature communications
Volume: 11(1)
Issue: 1
Pages: 4158-4158
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Polygenic architecture informs potential vulnerability to drug-induced liver injury2020
Author(s)
Koido M, Kawakami E, Fukumura J, Noguchi Y, Ohori M, Nio Y, Nicoletti P, Aithal GP, Daly AK, Watkins PB, Anayama H, Dragan Y, Shinozawa T, Takebe T.
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Journal Title
Nature Medicine
Volume: 26
Issue: 10
Pages: 1541-1548
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Generation of human induced pluripotent stem cell-derived liver buds with chemically defined and animal origin-free media2020
Author(s)
Sekine K, Ogawa S, Tsuzuki S, Kobayashi T, Ikeda K, Nakanishi N, Takeuchi K, Kanai E, Otake Y, Okamoto S, Kobayashi T, Takebe T, Taniguchi H.
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Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 17937-17937
DOI
Related Report
Peer Reviewed / Open Access
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