Crosstalk via ICAM-1 enhances supportive phenotype of stellate cells and drives hepatocyte proliferation in iPSC-derived hepatic organoids.

IF 5.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Reports Pub Date : 2025-09-18 DOI:10.1016/j.stemcr.2025.102642

Tomohiro Mochida, Masato Miyoshi, Sei Kakinuma, Taro Shimizu, Jun Tsuchiya, Keiya Watakabe, Kento Inada, Shun Kaneko, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Mina Nakagawa, Mamoru Watanabe, Yasuhiro Asahina, Ryuichi Okamoto

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引用次数: 0

Abstract

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.

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在ipsc衍生的肝类器官中，通过ICAM-1的串扰增强星状细胞的支持表型并驱动肝细胞增殖。

肝星状细胞（HSC）与肝细胞之间的相互作用有助于HSC的活化和肝脏再生；然而，人类的机制尚不清楚，特别是它们直接接触的意义和细胞粘附分子的作用。在这项研究中，我们利用诱导多能干细胞（iPSC）衍生的肝星状细胞（ips - hsc）和肝细胞样细胞（iPS-Heps）建立了一种新的接触共培养类器官，称为iPSC衍生的肝细胞-星状细胞周围类器官（iHSOs）。ips - hsc在中心iPS-Heps周围表现出独特的形态。iHSO能够鉴定出icam -1-白细胞介素-1β (IL-1β)介导的iPS-HSCs支持的iPS-Hep增殖，其表现出静止和细胞因子丰富的表型，而这种增殖支持在原代肝细胞共培养的类器官中没有观察到。此外，对乙酰氨基酚处理的ihso可以模拟肝细胞损伤诱导的HSC活化，显示了其应用潜力。我们的研究为研究人类造血干细胞的行为以及造血干细胞与肝细胞之间复杂的相互作用提供了一个有价值的平台。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.