Development of hiPSC-organoid culture platform toward organ generation.

• Project/Area Number: 21H04830
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Taniguchi Hideki 東京大学, 医科学研究所, 教授 (70292555)
• Co-Investigator(Kenkyū-buntansha): 久世 祥己 東京大学, 医科学研究所, 特任研究員 (70837806) ; 村田 聡一郎 横浜市立大学, 医学部, 准教授 (40436275)
• Project Period (FY): 2021-04-05 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥42,510,000 (Direct Cost: ¥32,700,000、Indirect Cost: ¥9,810,000); Fiscal Year 2023: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000); Fiscal Year 2022: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000); Fiscal Year 2021: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
• Keywords: iPS細胞 / オルガノイド / 肝臓 / iPS

Outline of Research at the Start

本研究は、我々が世界に先駆けて開発に成功したヒトiPSC肝臓オルガノイドの創出法を大きく発展させることにより、血管吻合移植可能なヒト臓器創出技術の開発を目指すものである。すなわち、ヒトiPS細胞からの大血管創出技術などの要素技術開発を行い、大血管が付与されたオルガノイドを対象とした還流培養システムの開発を進めることにより、in vitroにおけるヒト臓器創出のための基盤的な研究プラットフォームの構築を試みる。

Outline of Final Research Achievements

This study aimed to develop a technique for the creation of human iPSC-blood vessel incorporated liver organoid toward the artificial generation of human organs.
(The results are not to be disclosed at this time and will be resubmitted at a later date.)

Academic Significance and Societal Importance of the Research Achievements

移植医療においてはドナー臓器の供給に明らかな限界が存在し、移植待機人数と実施件数の間に大きな解離が生じているのが現状である。当研究室では、世界に先駆けてヒトiPS細胞からオルガノイドを人為的に再構成する方法の開発に成功しており、ヒトiPSCオルガノイドを用いた移植医療の実現化に向けて、様々な技術開発を推進している。本研究では、オルガノイド作製技術を応用したヒト臓器創出法の開発を目指して、オルガノイド培養に関連する新規基盤技術を構築した。本技術は、我々が研究対象としている肝臓のみならず、膵臓や腎臓など全ての臓器に適応することが可能であり、極めて高い波及効果が期待される。

Research Products

• [Journal Article] Highly Sensitive Detection of Human Pluripotent Stem Cells by Loop-Mediated Isothermal Amplification (2022)
  • Author(s): Yasui Ryota、Matsui Atsuka、Sekine Keisuke、Okamoto Satoshi、Taniguchi Hideki
  • Journal Title: Stem Cell Reviews and Reports Volume: 18 Issue: 8 Pages: 2995-3007
  • DOI: 10.1007/s12015-022-10402-3
  • Peer Reviewed / Open Access
• [Journal Article] Mechanical guidance of self-condensation patterns of differentiating progeny (2022)
  • Author(s): Matsuzaki Takahisa、Shimokawa Yuko、Koike Hiroyuki、Kimura Masaki、Kawano Yuma、Okuma Nao、Kawamura Ryuzo、Yoneyama Yosuke、Furuichi Yasuro、Hakuno Fumihiko、Takahashi Shin-Ichiro、Nakabayashi Seiichiro、Okamoto Satoshi、Nakauchi Hiromitsu、Taniguchi Hideki、Takebe Takanori、Yoshikawa Hiroshi Y.
  • Journal Title: iScience Volume: 25 Issue: 10 Pages: 105109-105109
  • DOI: 10.1016/j.isci.2022.105109
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Stabilized generation of human iPSC-derived liver organoids using a modified coating approach (2022)
  • Author(s): Kamishibahara Yu、Okamoto Satoshi、Ohkuma Takuya、Taniguchi Hideki
  • Journal Title: Biology Methods and Protocols Volume: 8 Issue: 1
  • DOI: 10.1093/biomethods/bpac034
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of a mouse model of pancreatic cancer using human pancreatic cancer cell line S2-013-derived organoid. (2022)
  • Author(s): Tanaka C, Furihata K, Naganuma S, Ogasawara M, Yoshioka R, Taniguchi H, Furihata M, Taniuchi K
  • Journal Title: Human cell. Volume: 35(2) Issue: 2 Pages: 735-744
  • DOI: 10.1007/s13577-022-00684-7
  • Peer Reviewed / Open Access
• [Journal Article] Improving the repopulation capacity of elderly human hepatocytes by decoding aging-associated hepatocyte plasticity. (2022)
  • Author(s): Nie YZ, Zheng YW, Taniguchi H
  • Journal Title: Hepatology Volume: 0 Issue: 4 Pages: 0-0
  • DOI: 10.1002/hep.32443
  • Peer Reviewed / Open Access
• [Journal Article] Development of the nervous system in mouse liver. (2022)
  • Author(s): Koike N, Tadokoro T, Ueno Y, Okamoto S, Kobayashi T, Murata S, Taniguchi H
  • Journal Title: World Journal of Hepatology Volume: 14 Issue: 2 Pages: 386-399
  • DOI: 10.4254/wjh.v14.i2.386
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of immunosuppression protocols for MHC-matched allogeneic iPS cell-based transplantation using a mouse skin transplantation model. (2022)
  • Author(s): Kamatani T, Otsuka R, Murata T, Wada H, Takahashi T, Mori A, Murata S, Taniguchi H, Seino KI.
  • Journal Title: Inflammation and Regeneration Volume: 42 Issue: 1 Pages: 4-4
  • DOI: 10.1186/s41232-021-00190-7
  • Peer Reviewed / Open Access
• [Journal Article] Clever Experimental Designs: Shortcuts for Better iPSC Differentiation. (2021)
  • Author(s): Yasui R, Sekine K, Taniguchi H.
  • Journal Title: Cells Volume: 10 Issue: 12 Pages: 3540-3540
  • DOI: 10.3390/cells10123540
  • Peer Reviewed / Open Access
• [Journal Article] Serous Membrane Detachment with Ultrasonic Homogenizer Improves Engraftment of Fetal Liver to Liver Surface in a Rat Model of Cirrhosis. (2021)
  • Author(s): Kawakatsu-Hatada Y,Murata S,Mori A,Kimura K,Taniguchi H.
  • Journal Title: International Journal of Molecular Sciences Volume: 22 Issue: 21 Pages: 11589-11589
  • DOI: 10.3390/ijms222111589
  • Peer Reviewed / Open Access
• [Journal Article] Human Pluripotent Stem Cell-Derived Hepatocyte-Like Cells and Organoids for Liver Disease and Therapy (2021)
  • Author(s): Li Y, Yang X, Plummer R, Hayashi Y, Deng XS, Nie YZ, Taniguchi H
  • Journal Title: International Journal of Molecular Sciences Volume: 22 Issue: 19 Pages: 10471-10471
  • DOI: 10.3390/ijms221910471
  • Peer Reviewed / Open Access
• [Journal Article] Dorso-ventral heterogeneity in tracheal basal stem cells. (2021)
  • Author(s): Tadokoro T, Tanaka K, Osakabe S, Kato M, Kobayashi H, Hogan BLM, Taniguchi H.
  • Journal Title: Biology Open Volume: 10 Issue: 9
  • DOI: 10.1242/bio.058676
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A novel orthotopic liver cancer model for creating human-like tumor microenvironment. (2021)
  • Author(s): Qiu R, Murata S, Cheng C, Mori A, Nie Y, Mikami S, Hasegawa S, Tadokoro T, Okamoto S, Taniguchi H.
  • Journal Title: Cancers(Basel) Volume: 13 Issue: 16 Pages: 3997-3997
  • DOI: 10.3390/cancers13163997
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Robust parameter design of human induced pluripotent stem cell differentiation protocols defines lineage-specific induction of anterior-posterior gut tube endodermal cells. (2021)
  • Author(s): Yasui R, Sekine K, Yamaguchi K, Furukawa Y, Taniguchi H
  • Journal Title: Stem Cells Volume: 39 Issue: 4 Pages: 429-442
  • DOI: 10.1002/stem.3326
  • Peer Reviewed / Open Access
• [Presentation] Development of innovative regenerative therapies for liver disease using human iPS cells (2022)
  • Author(s): 谷口 英樹
  • Organizer: The 34th Meeting of Japanese Society of Hepato-Biliary-Pancreatic Surgery
  • Int'l Joint Research / Invited
• [Presentation] ヒトiPS細胞肝臓オルガノイドの脱細胞化骨格への充填による肝組織再構築法の開発 (2022)
  • Author(s): 山邊 聡一郎、久世 祥己、松尾 めぐみ、奥村 高志、河西 利治、西 晃太郞、土田 倫範、森作 俊紀、八木 洋、谷口 英樹
  • Organizer: 第99回日本生理学会
• [Presentation] ヒトiPS細胞オルガノイドを用いた新規肝疾患治療法の開発 (2021)
  • Author(s): 谷口英樹
  • Organizer: 第121回日本外科学会
• [Presentation] ヒトiPS細胞オルガノイドを用いた新規肝疾患治療法の開発 (2021)
  • Author(s): 谷口英樹
  • Organizer: 第115回日本消化器病学会四国支部例会
  • Invited
• [Presentation] ヒトiPS細胞オルガノイドを用いた新規肝疾患治療法の開発 (2021)
  • Author(s): 谷口英樹
  • Organizer: 日本消化器学会関東支部第366回例会
  • Invited
• [Presentation] Generation of human liver using iPS cells for regenerative therapies. (2021)
  • Author(s): 谷口英樹
  • Organizer: アジア太平洋肝臓学会シングルトピックカンファレンス大阪
  • Int'l Joint Research / Invited
• [Presentation] ヒトiPS細胞を用いた抗加齢医学研究 (2021)
  • Author(s): 谷口英樹
  • Organizer: 第21回日本抗加齢医学会総会
  • Invited
• [Presentation] Recapitulation of hepatic hematopoiesis with human liver organoids. (2021)
  • Author(s): Li Yang, Taniguchi Hideki, et al.,
  • Organizer: ISSCR 2021 Virtual Annual Meeting
  • Int'l Joint Research
• [Presentation] Generation of quiescent hepatic stellate cells from human induced pluripotent stem cells. (2021)
  • Author(s): Yang Xia, Taniguchi Hideki, et al
  • Organizer: ISSCR 2021 Virtual Annual Meeting.
  • Int'l Joint Research
• [Presentation] In-vitro generation of a functional and vascularized liver organoid from human iPS cells. (2021)
  • Author(s): Plummer RT, Taniguchi Hideki, et al.
  • Organizer: ISSCR Tokyo 2021 International Symposium Virtual.
  • Int'l Joint Research