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

Yoshiki Kuse, Shinya Matsumoto, Syusaku Tsuzuki, Erica Carolina, Takashi Okumura, Toshiharu Kasai, Soichiro Yamabe, Kiyoshi Yamaguchi, Yoichi Furukawa, Tomomi Tadokoro, Yasuharu Ueno, Takayoshi Oba, Naoki Tanimizu and Hideki Taniguchi ()
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Yoshiki Kuse: The University of Tokyo
Shinya Matsumoto: The University of Tokyo
Syusaku Tsuzuki: The University of Tokyo
Erica Carolina: The University of Tokyo
Takashi Okumura: The University of Tokyo
Toshiharu Kasai: The University of Tokyo
Soichiro Yamabe: The University of Tokyo
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

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-57551-w

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