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Placenta-derived factors contribute to human iPSC-liver organoid growth

Author

Listed:
  • Yoshiki Kuse

    (The University of Tokyo
    Gifu Pharmaceutical University)

  • Shinya Matsumoto

    (The University of Tokyo)

  • Syusaku Tsuzuki

    (The University of Tokyo)

  • Erica Carolina

    (The University of Tokyo
    Computational Biology and Medical Science)

  • Takashi Okumura

    (The University of Tokyo)

  • Toshiharu Kasai

    (The University of Tokyo)

  • Soichiro Yamabe

    (The University of Tokyo
    Computational Biology and Medical Science)

  • Kiyoshi Yamaguchi

    (The University of Tokyo)

  • Yoichi Furukawa

    (The University of Tokyo)

  • Tomomi Tadokoro

    (Yokohama City University Graduate School of Medicine)

  • Yasuharu Ueno

    (The University of Tokyo)

  • Takayoshi Oba

    (The University of Tokyo)

  • Naoki Tanimizu

    (The University of Tokyo)

  • Hideki Taniguchi

    (The University of Tokyo
    Yokohama City University Graduate School of Medicine)

Abstract

Organoids derived from human induced pluripotent stem cells (hiPSC) are potentially applicable for regenerative medicine. However, the applications have been hampered by limited organoid size and function as a consequence of a lack of progenitor expansion. Here, we report the recapitulation of progenitor expansion in hiPSC-liver organoids based on the analysis of mouse development. Visualization of blood perfusion and oxygen levels in mouse embryos reveals a transient hypoxic environment during hepatoblast expansion, despite active blood flow. During this specific stage, the placenta expresses various growth factors. Human and mouse placenta-liver interaction analysis identifies various placenta-derived factors. Among them, IL1α efficiently induces the growth in hiPSC-liver organoids as well as mouse fetal livers following progenitor expansion under hypoxia. Furthermore, subsequent oxygenation demonstrates that progenitors expanded by IL1α contribute to hiPSC-liver organoid size and function. Taken together, we demonstrate that treatment with the placenta-derived factor under hypoxia is a crucial human organoid culture technique that efficiently induces progenitor expansion.

Suggested Citation

  • Yoshiki Kuse & Shinya Matsumoto & Syusaku Tsuzuki & Erica Carolina & Takashi Okumura & Toshiharu Kasai & Soichiro Yamabe & Kiyoshi Yamaguchi & Yoichi Furukawa & Tomomi Tadokoro & Yasuharu Ueno & Takay, 2025. "Placenta-derived factors contribute to human iPSC-liver organoid growth," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57551-w
    DOI: 10.1038/s41467-025-57551-w
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    References listed on IDEAS

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    1. David Willnow & Uwe Benary & Anca Margineanu & Maria Lillina Vignola & Fabian Konrath & Igor M. Pongrac & Zahra Karimaddini & Alessandra Vigilante & Jana Wolf & Francesca M. Spagnoli, 2021. "Quantitative lineage analysis identifies a hepato-pancreato-biliary progenitor niche," Nature, Nature, vol. 597(7874), pages 87-91, September.
    2. J. Gray Camp & Keisuke Sekine & Tobias Gerber & Henry Loeffler-Wirth & Hans Binder & Malgorzata Gac & Sabina Kanton & Jorge Kageyama & Georg Damm & Daniel Seehofer & Lenka Belicova & Marc Bickle & Ric, 2017. "Multilineage communication regulates human liver bud development from pluripotency," Nature, Nature, vol. 546(7659), pages 533-538, June.
    3. Takanori Takebe & Keisuke Sekine & Masahiro Enomura & Hiroyuki Koike & Masaki Kimura & Takunori Ogaeri & Ran-Ran Zhang & Yasuharu Ueno & Yun-Wen Zheng & Naoto Koike & Shinsuke Aoyama & Yasuhisa Adachi, 2013. "Vascularized and functional human liver from an iPSC-derived organ bud transplant," Nature, Nature, vol. 499(7459), pages 481-484, July.
    4. Tomoyuki Yamaguchi & Hideyuki Sato & Megumi Kato-Itoh & Teppei Goto & Hiromasa Hara & Makoto Sanbo & Naoaki Mizuno & Toshihiro Kobayashi & Ayaka Yanagida & Ayumi Umino & Yasunori Ota & Sanae Hamanaka , 2017. "Interspecies organogenesis generates autologous functional islets," Nature, Nature, vol. 542(7640), pages 191-196, February.
    5. Inês Godet & Yu Jung Shin & Julia A. Ju & I Chae Ye & Guannan Wang & Daniele M. Gilkes, 2019. "Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    6. Linda Lorenz & Jennifer Axnick & Tobias Buschmann & Carina Henning & Sofia Urner & Shentong Fang & Harri Nurmi & Nicole Eichhorst & Richard Holtmeier & Kálmán Bódis & Jong-Hee Hwang & Karsten Müssig &, 2018. "Mechanosensing by β1 integrin induces angiocrine signals for liver growth and survival," Nature, Nature, vol. 562(7725), pages 128-132, October.
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