Method for preparing quiescent hepatic stellate cells and a model for evaluating their activation.

A method for differentiating pluripotent stem cells into quiescent hepatic stellate cells using three-dimensional culture and low oxygen concentration with a Rock inhibitor addresses the lack of suitable quiescent cells, enabling drug screening for liver diseases by maintaining a stable quiescent state and evaluating activation.

JP7884857B2Active Publication Date: 2026-07-06THE UNIV OF TOKYO
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Patent Information

Authority / Receiving Office
JP Β· JP
Patent Type
Patents
Current Assignee / Owner
THE UNIV OF TOKYO
Filing Date
2024-07-16
Publication Date
2026-07-06

AI Technical Summary

Technical Problem

Existing methods fail to provide a sufficient quantity of quiescent hepatic stellate cells for drug discovery screening systems, as commercially available cells are already activated, and primary cultured hepatic stellate cells are not suitable for research and development of drugs targeting liver fibrosis.

Method used

A method is developed to differentiate pluripotent stem cells, such as iPS cells, into quiescent hepatic stellate cells through three-dimensional culture and low oxygen concentration, incorporating a Rock inhibitor, and using a reporter gene to maintain a quiescent state, allowing for the isolation and screening of drugs that suppress hepatic stellate cell activation.

Benefits of technology

The method enables the production of stable quiescent hepatic stellate cells for drug screening, facilitating the development of therapeutic drugs for liver diseases like cirrhosis by maintaining a quiescent state and enabling effective activation evaluation.

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Abstract

To provide a method for preparing quiescent hepatic stellate cells by inducing differentiation of pluripotent stem cells, and to provide a method for screening drugs involved in the activation of quiescent hepatic stellate cells.SOLUTION: According to the present invention, there is provided a method for preparing quiescent hepatic stellate cells, which includes a step of inducing differentiation of iPS cells and isolating quiescent hepatic stellate cells using an NGFR-positive phenotype as an indicator. In addition, there is provided a screening method for selecting a candidate substance for use in a drug for treating or preventing liver disease accompanied by fibrosis based on the expression level of a gene marker that is specifically expressed in activated hepatic stellate cells by introducing a reporter gene into the quiescent hepatic stellate cells.SELECTED DRAWING: Figure 1
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Citation Information

Patent Citations

  • CN104232588A

  • WO2016148216A1