Optimized Ex Vivo Human Liver Slice Culture Maintains Extended Viability and Function for Hepatotoxicity Testing

Area of Science:

• Hepatology
• Toxicology
• Ex vivo models

Background:

• Human precision-cut liver slices (hPCLS) are valuable for liver research but have limited viability.
• Short lifespan restricts long-term functional studies and drug testing.

Purpose of the Study:

• To develop an optimized ex vivo culture system (hPCLS-EV) for extended viability of human liver slices.
• To maintain tissue viability, cellular composition, and liver-specific functions for up to five days.

Main Methods:

• Optimized culture conditions including reduced slice thickness, high oxygen, and air-liquid interface.
• Assessed tissue viability, cellular composition, and liver-specific functions over five days.
• Utilized transcriptomic profiling and drug-induced liver injury (DILI) modeling.

Main Results:

• hPCLS-EV maintained tissue viability, cellular integrity, and immune cell populations for five days.
• Sustained albumin secretion, glutathione content, and CYP450 activity were confirmed.
• Transcriptomic analysis showed pathway stabilization by day 5 with limited fibrosis.
• The model accurately reflected acetaminophen and troglitazone induced liver injury patterns.

Conclusions:

• Optimized hPCLS-EV is a robust ex vivo human liver model with extended functionality.
• Enables longitudinal assessment of hepatotoxic injury and drug effects.
• Provides a valuable platform for preclinical toxicity testing and precision medicine applications.