Liver Organoids: From Disease Modelling to Regenerative Medicine

Area of Science:

• Biotechnology
• Regenerative Medicine
• Hepatology

Background:

• Liver organoids are 3D in vitro models mimicking human liver structure and function.
• They serve as powerful platforms for research and clinical applications.

Purpose of the Study:

• To systematically review liver organoid fabrication, disease modeling, and regenerative potential.
• To identify challenges and future directions in the field.

Main Methods:

• Endothelial co-culture for vascularized and zonated organoids.
• Prime editing for precise mutation correction in patient-derived organoids.
• Integration of iPSC-derived liver organoids for disease modeling and drug screening.

Main Results:

• Successful generation of vascularized liver organoids with >85% endothelial coverage.
• Precise correction of mutations using prime editing with no detected off-target effects.
• Faithful recapitulation of metabolic dysfunction-associated steatotic liver disease (MASLD) and validation of semaglutide efficacy.
• Development of macrophage-integrated models for viral life cycle studies and antiviral screening.
• Establishment of tumor organoid biobanks preserving cancer heterogeneity and drug resistance.
• Demonstration of therapeutic potential in animal models for acute liver failure and genetic disorders.

Conclusions:

• Liver organoids offer significant potential for precision hepatology and regenerative therapies.
• Key challenges include hepatocyte maturity, vascular network construction, and standardization of protocols.
• Continued interdisciplinary efforts are crucial for clinical translation.