A human-based iPSC-derived liver organoid, or iHSO, forms 3D co-cultures of hepatocyte-like and stellate-like cells with stellate cells surrounding hepatocytes, enabling study of liver repair, fibrosis, and potential drug therapies.

The model reveals signaling between hepatic stellate cells and hepatocytes, especially the ICAM-1–IL-1β axis, showing quiescent stellate cells can support hepatocyte proliferation but may drive fibrosis if dysregulated.

When exposed to acetaminophen, the organoids mimic liver injury and stellate cell activation patterns seen in humans, underscoring its relevance for researching fibrosis and regeneration.

Chronic liver disease affects more than four million adults in the United States, with rising cases in Japan highlighting the need for therapies that prevent or reverse fibrosis rather than relying solely on transplantation.

The study was led by Prof. Sei Kakinuma, Prof. Yasuhiro Asahina, Assistant Prof. Masato Miyoshi, and graduate student Tomohiro Mochida at Science Tokyo, in collaboration with Juntendo University, and published in Stem Cell Reports on September 18, 2025.

The work, titled Crosstalk via ICAM-1 enhances supportive phenotype of stellate cells and drives hepatocyte proliferation in iPSC-derived hepatic organoids, was published by Science Tokyo and Juntendo University researchers in Stem Cell Reports.

The research team comprises Professors Sei Kakinuma and Yasuhiro Asahina, with Masato Miyoshi and Tomohiro Mochida, and was published on September 18, 2025.

Targeting ICAM-1 and IL-1β pathways could modulate stellate cell behavior to delay or reverse fibrosis and reduce dependence on transplantation.

The organoid provides a scalable, human-relevant platform to study fibrosis progression and test anti-fibrotic therapies, potentially offering greater predictive value than animal models.

Beyond disease modeling, the system could inform regenerative medicine and bioartificial liver development by exploring stellate cell heterogeneity and its influence on hepatocyte survival and proliferation.