2025-09-19 東京科学大学
図1. ヒトiPS細胞由来の肝細胞と肝星細胞による新たな肝臓オルガノイド:iHSO
<関連情報>
- https://www.isct.ac.jp/ja/news/e5e80tn0cq2l
- https://www.isct.ac.jp/plugins/cms/component_download_file.php?type=2&pageId=&contentsId=1&contentsDataId=2297&prevId=&key=7fc993c54ebd767709cda0d645b5f785.pdf
- https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(25)00246-2
ICAM-1を介したクロストークは、iPS細胞由来肝臓オルガノイドにおいて星状細胞の支持的表現型を増強し、肝細胞の増殖を促進する Crosstalk via ICAM-1 enhances supportive phenotype of stellate cells and drives hepatocyte proliferation in iPSC-derived hepatic organoids
Tomohiro Mochida ∙ Masato Miyoshi ∙ Sei Kakinuma ∙ … ∙ Mamoru Watanabe ∙ Yasuhiro Asahina ∙ Ryuichi Okamoto
Stem Cell Reports Published:September 18, 2025
DOI:https://doi.org/10.1016/j.stemcr.2025.102642
Highlights
- We established iHSOs, a new human iPSC-derived hepatic organoids
- iPS-HSCs in iHSOs show quiescent, cytokine-rich phenotype not seen in monoculture
- Crosstalk via ICAM-1-IL-1β allows HSCs to support hepatocyte proliferation in iHSOs
- iHSOs can be applied to model liver injury and stellate cell activation in vitro
Summary
The interaction between hepatic stellate cells (HSCs) and hepatocytes contributes to HSC activation and liver regeneration; however, the mechanisms in humans remain unclear, particularly the significance of their direct contact and the role of cell adhesion molecules. In this study, we established a novel contact co-culture organoids using induced pluripotent stem cell (iPSC)-derived hepatic stellate-like cells (iPS-HSCs) and hepatocyte-like cells (iPS-Heps), termed iPSC-derived hepatocyte-stellate cell surrounding organoids (iHSOs). The iHSOs exhibit a unique morphology with iPS-HSCs surrounding central iPS-Heps. The iHSO enabled the identification of ICAM-1-interleukin-1β (IL-1β)-mediated iPS-Hep proliferation supported by iPS-HSCs, which displayed a quiescent and cytokine-rich phenotype, whereas this proliferative support was not observed in primary liver cell-based co-culture organoids. Furthermore, iHSOs treated with acetaminophen allowed for the modeling of HSC activation induced by hepatocyte injury, demonstrating their application potential. Our study presents a valuable platform for studying the HSC behavior and complex interactions between HSCs and hepatocytes in humans.
