In vivo mass culture system of human iPS cell-derived hepatocytes
Project/Area Number |
18KK0307
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Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 90:Biomedical engineering and related fields
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Research Institution | The University of Tokyo (2019-2022) Osaka University (2018) |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
吉見 一人 東京大学, 医科学研究所, 講師 (50709813)
武石 一樹 九州大学, 大学病院, 特別教員 (50733713)
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Project Period (FY) |
2018-10-09 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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Keywords | ヒト肝細胞 / iPS細胞 / 免疫不全ラット / ゲノム編集 / 肝移植 |
Outline of Final Research Achievements |
Using the iPS-Heps culture protocol developed by the University of Pittsburgh, we were able to culture a large number of human iPS-Heps cells in the livers of immunodeficient rats through cell transplantation. To recover a significant amount of proliferated iPS-Heps from within the rat liver, we generated immunodeficient rats transgenic with iCasp9 as a suicide gene, but we were unable to confirm cell death in the rat liver. Instead, we successfully produced severe immunodeficient rats with a knock-in of human SIRPA or KIT genes. By inducing the death of hepatocytes in these severe immunodeficient rats, we will establish a method to exclusively generate human iPS-Heps cells in vivo within immunodeficient rats.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、Bioreactorとしてラット肝臓内でiPS-Hepsを成熟させ、ヒト肝細胞を大量に作り出す方法を確立する。肝不全に対する革新的新規治療法を開発するだけでなく、創薬でのヒト肝細胞の大量利用を実現する。
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Report
(6 results)
Research Products
(90 results)
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[Journal Article] 2. Highly selective transgene expression through the flip-excision switch system by using a unilateral spacer sequence.2023
Author(s)
Matsushita, N.*, Kato, S.*, Nishizawa, K., Sugawara, M., Takeuchi, K., Miyasaka, Y., Mashimo, T. and Kobayashi, K. * Equal contribution
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Journal Title
Cell Rep. Methods
Volume: 3
Issue: 2
Pages: 100393-100393
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A heterozygous LAMA5 variant may contribute to slowly progressive, vinculin-enhanced familial FSGS and pulmonary defects.2022
Author(s)
Kaimori JY, Kikkawa Y, Motooka D, Namba-Hamano T, Takuwa A, Okazaki A, Kobayashi K, Tanigawa A, Kotani Y, Uno Y, Yoshimi K, Hattori K, Asahina Y, Kajimoto S, Doi Y, Oka T, Sakaguchi Y, Mashimo T, Sekiguchi K, Nakaya A, Nomizu M, Isaka Y.
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Journal Title
JCI insight
Volume: 7
Issue: 23
Pages: 522-524
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 3. Catecholaminergic cell type-specific expression of Cre recombinase in knock-in transgenic rats generated by the Combi-CRISPR technology.2022
Author(s)
Matsushita, N., Nishizawa, K., Kato, S., Iguchi, Y., Fukabori, R., Takeuchi, K., Miyasaka, Y., Mashimo, T. and Kobayashi, K.
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Journal Title
J. Neurosci. Methods
Volume: 381
Pages: 109707-109707
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Brca1^L63X/+ rat is a novel model of human BRCA1 deficiency displaying susceptibility to radiation-induced mammary cancer2022
Author(s)
Yuzuki Nakamura, Jo Kubota, Yukiko Nishimura, Kento Nagata, Mayumi Nishimura, Kazuhiro Daino, Atsuko Ishikawa, Takehito Kaneko, Tomoji Mashimo, Toshiaki Kokubo, Masaru Takabatake, Kazumasa Inoue, Masahiro F
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Journal Title
Cancer science
Volume: 113
Issue: 10
Pages: 3362-3375
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CRISPR-mediated Bmpr2 point mutation exacerbates late pulmonary vasculopathy and reduces survival in rats with experimental pulmonary hypertension2022
Author(s)
Kabwe JC, Sawada H, Mitani Y, Oshita H, Tsuboya N, Zhang E, Maruyama J, Miyasaka Y, Ko H, Oya K, Ito H, Yodoya N, Otsuki S, Ohashi H, Okamoto R, Dohi K, Nishimura Y, Mashimo T, Hirayama M, Maruyama K.
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Journal Title
Respir Res.
Volume: ;23
Issue: 1
Pages: 1-22
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Impact of GAD65 and/or GAD67 deficiency on perinatal development in rats.2022
Author(s)
Jiang W, Kakizaki T, Fujihara K, Miyata S, Zhang Y, Suto T, Kato D, Saito S, Shibasaki K, Ishizaki Y, Isoda K, Yokoo H, Obinata H, Hirano T, Miyasaka Y, Mashimo T, Yanagawa Y.
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Journal Title
.FASEB J .
Volume: 36(2)
Issue: 2
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Study of the CRISPR/Cas3 System for Xenotransplantation2022
Author(s)
Miyagawa S, Watanabe M, Nagashima H, Sato K, Kogata S, Toyama C, Masahata K, Kamiyama M, Yamamoto R, Eguchi H, Maeda A, Yoshimi K, Mashimo T, Okuyama H.
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Journal Title
Transplant Proc
Volume: 54
Issue: 2
Pages: 522-524
DOI
Related Report
Peer Reviewed
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[Journal Article] PHF24 is expressed in the inhibitory interneurons in rats2021
Author(s)
Numakura Yuki、Uemura Risa、Tanaka Miyuu、Izawa Takeshi、Yamate Jyoji、Kuramoto Takashi、Kaneko Takehito、Mashimo Tomoji、Yamamoto Takashi、Serikawa Tadao、Kuwamura Mitsuru
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Journal Title
Experimental Animals
Volume: 70
Issue: 1
Pages: 137-143
DOI
NAID
ISSN
0007-5124, 1341-1357, 1881-7122
Related Report
Peer Reviewed
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[Journal Article] Down syndrome cell adhesion molecule like-1 (DSCAML1) links the GABA system and seizure susceptibility.2020
Author(s)
Hayase Y, Amano S, Hashizume K, Tominaga T, Miyamoto H, Kanno Y, Ueno-Inoue Y, Inoue T, Yamada M, Ogata S, Balan S, Hayashi K, Miura Y, Tokudome K, Ohno Y, Nishijo T, Momiyama T, Yanagawa Y, Takizawa A, Mashimo T, Serikawa T, Sekine A, Nakagawa E, Takeshita E, Yoshikawa T, Waga C, Inoue K, Goto YI, Nabeshima Y, et al.
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Journal Title
Acta Neuropathol Commun.
Volume: 8
Issue: 1
Pages: 206-206
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 効率的なゲノム編集ラットの作製方法2020
Author(s)
服部晃佑、吉見一人、松下夏樹、小林和人、真下知士
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Journal Title
マウス・ラットモデル作製・解析プロフェッショナル. あなたの研究をステップアップさせる最新・最適手技. 先端モデル動物支援プラットフォーム(AdAMS)
Volume: -
Pages: 54-63
Related Report
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[Journal Article] Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair2020
Author(s)
Nakazawa Y, Hara Y, Oka Y, Komine O, van den Heuvel D, Guo C, Daigaku Y, Isono M, He Y, Shimada M, Kato K, Jia N, Hashimoto S, Kotani Y, Miyoshi Y, Tanaka M, Sobue A, Mitsutake N, Suganami T, Masuda A, Ohno K, Nakada S, Mashimo T, Yamanaka K, Luijsterburg MS, Ogi T
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Journal Title
Cell
Volume: 19
Issue: 6
Pages: 1228-1244
DOI
NAID
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Pathological characteristics of <i>Ccdc85c</i> knockout rats: a rat model of genetic hydrocephalus2020
Author(s)
Konishi S, Tanaka N, Mashimo T, Yamamoto T, Sakuma T, Kaneko T, Tanaka M, Izawa T, Yamate J, Kuwamura M
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Journal Title
Experimental Animals
Volume: 69
Issue: 1
Pages: 26-33
DOI
NAID
ISSN
0007-5124, 1341-1357, 1881-7122
Related Report
Peer Reviewed / Open Access
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[Book] 腫瘍内科2023
Author(s)
藤井智明、真下知士
Total Pages
123
Publisher
科学評論社
Related Report
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[Book] 再生医療2022
Author(s)
吉見一人、真下知士
Total Pages
57
Publisher
日本再生医療学会雑誌
Related Report
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