Engineered Liver Platforms for Different Phases of Drug Development

Area of Science:

• Hepatology and Toxicology
• Biomedical Engineering
• Drug Development Science

Background:

• Drug-induced liver injury (DILI) is a major reason for drug withdrawal.
• Species-specific liver pathways necessitate accurate human DILI prediction models.
• In vitro human liver models are crucial for assessing drug safety.

Purpose of the Study:

• To review engineered human liver platforms for drug development.
• To highlight the role of microfabrication in stabilizing liver functions.
• To discuss the application of these models across different drug development phases.

Main Methods:

• Utilizing microfabrication for precise control over cellular microenvironments.
• Engineering human liver models with varying complexity using diverse cell sources (cell lines, primary cells, stem cell-derived hepatocytes).
• Incorporating multiple human liver cell types and organ-on-a-chip systems to mimic in vivo interactions and multi-organ toxicities.

Main Results:

• Engineered liver models can stabilize human liver functions for extended periods.
• Models incorporating multiple cell types can replicate specific DILI mechanisms.
• Organ-on-a-chip platforms reveal liver-specific drug metabolism impacts on systemic toxicity.

Conclusions:

• Engineered human liver models offer a powerful tool for predicting DILI.
• These platforms enhance the reliability of preclinical drug safety assessments.
• The review provides a comprehensive overview of available platforms for various drug development stages.