[Effect evaluation of three cell culture models].

Area of Science:

• Hepatocyte culture models
• Drug metabolism and toxicology
• Biochemical assays

Context:

• Primary rat hepatocytes are crucial for studying drug metabolism and toxicity.
• Evaluating different in vitro culture systems (monolayer, sandwich, bioreactor) is essential for accurate toxicological and pharmacological assessments.
• Understanding hepatocyte function over time in culture informs the choice of model for specific research questions.

Purpose:

• To compare the suitability of monolayer culture (MC), sandwich culture (SC), and bioreactor systems for culturing primary rat hepatocytes.
• To assess key indicators of hepatocyte viability and function, including enzyme leakage (LDH, AST, ALT), albumin secretion, and cytochrome P450 1A (CYP 1A) activity.
• To evaluate the impact of CYP450 inducers on CYP 1A activity across the different culture models.

Summary:

• Bioreactor cultures maintained stable CYP 1A activity for over two weeks, outperforming MC and SC where activity declined over time.
• Albumin production was highest in bioreactors, followed by SC and MC.
• While MC showed increased LDH leakage after 5 days and SC showed none after 8 days, both MC and SC exhibited faster CYP 1A decline compared to bioreactors.
• CYP 1A induction by omeprazole and 3-methylcholanthrene was observed in all models, with higher induction in MC than SC.

Impact:

• The findings highlight the distinct advantages and disadvantages of each in vitro hepatocyte model.
• Bioreactor systems demonstrate superior long-term maintenance of hepatocyte function, particularly CYP 1A activity and albumin production.
• The choice of culture model significantly influences experimental outcomes in drug metabolism and toxicology research, guiding researchers towards optimal systems for their specific investigations.