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Updated: May 3, 2026

Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells
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Human assembloids recapitulate periportal liver tissue in vitro.

Lei Yuan1, Sagarika Dawka1, Yohan Kim1,2

  • 1Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.

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|December 17, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed patient-specific human hepatocyte organoids (h-HepOrgs) for long-term liver cell expansion. These organoids and derived liver assembloids enable in vitro disease modeling and drug discovery.

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Area of Science:

  • Hepatology
  • Tissue Engineering
  • Regenerative Medicine

Background:

  • In vitro models for human liver disease and drug discovery are limited.
  • In vitro expansion of primary human hepatocytes has not been achieved.
  • Complex multicellular liver systems are crucial for disease modeling and tissue engineering.

Purpose of the Study:

  • To develop patient-specific human hepatocyte organoids (h-HepOrgs) for in vitro liver research.
  • To create patient-specific periportal liver assembloids for advanced disease modeling.
  • To establish a novel platform for liver pathophysiology investigation and personalized medicine.

Main Methods:

  • Developed patient-derived human hepatocyte organoids (h-HepOrgs) from 28 individuals.
  • Maintained long-term hepatocyte expansion, preserving patient-specific gene expression and function.
  • Generated periportal liver assembloids by combining h-HepOrgs with mesenchyme and cholangiocyte organoids.

Main Results:

  • h-HepOrgs demonstrated sustained in vitro expansion and maintained in vivo characteristics.
  • Transplanted h-HepOrgs rescued a mouse model of liver disease.
  • Liver assembloids accurately recapitulated periportal liver tissue structure and cell interactions.

Conclusions:

  • Patient-derived h-HepOrgs and liver assembloids provide a powerful in vitro platform.
  • This system facilitates the study of liver pathophysiology, including biliary fibrosis.
  • The platform supports drug development, early diagnosis, and personalized liver medicine.