[Liver organ systems: valuation by gene expression]

Area of Science:

• Hepatology
• In vitro toxicology
• Organ culture technology

Background:

• Liver functions rely on complex hepatocyte interactions within intact structures.
• Current in vitro liver models use single cells, disrupting organ architecture.
• Existing liver slice culture methods are limited to short-term studies with general viability assessments.

Purpose of the Study:

• To develop and validate a novel interphase system for long-term precision-cut liver slice (PCLS) culture.
• To establish liver-specific gene expression as a robust viability criterion for PCLS.
• To demonstrate the superiority of the interphase system over perfusion systems for liver research.

Main Methods:

• Utilized precision-cut liver slices (PCLS) to maintain intact liver architecture.
• Developed an interphase culture system for long-term PCLS maintenance.
• Assessed liver viability by monitoring the regulation of liver-specific gene expression in response to stimuli.

Main Results:

• The interphase system demonstrated superior performance compared to perfusion systems in maintaining liver viability.
• Hormonal responsiveness of PCLS in the interphase system mirrored in vivo conditions.
• Long-term cultures showed modulated liver-specific gene expression (dexamethasone, cAMP, endotoxin) consistent with in vivo responses.

Conclusions:

• The developed interphase system provides a standardized, economical, and easy-to-handle platform for long-term liver slice culture.
• Liver-specific gene expression regulation is a reliable indicator of viability in PCLS.
• This system offers a promising alternative to in vivo experiments for studying liver physiology and toxicology.