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Liver-Brain Model: Technical Data

Application Note, Validation Data, and Key Findings

Application Note

Modeling the Liver-Brain Axis with NANOSTACKS™

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This comprehensive note encompasses the characterization of differentiated HepaRG cells on NANOSTACKS™, providing insights into their behaviour and functionality. Additionally, it outlines the execution of neurotoxicity testing, shedding light on how NANOSTACKS™ facilitates the study of intercellular interactions and potential cross-effects between liver and brain cells.

Multiorgan toxicity data visualization

Key Findings

Validation data demonstrating model performance

Stable CYP3A4 Activity

1379Day00.040.080.15Normalized Activity

No statistically significant difference between timepoints, demonstrating maintained metabolic functionality.

Enhanced Sensitivity with Liver Component

Triculture (Liver-Brain)Monoculture (SH-SY5Y)00.0250.050.0750.1IC50 (µM)

Increased Sensitivity

26.8% lower IC50

The liver component increased the model's sensitivity to paclitaxel

Conclusions

HepaRG® Cell Performance

  • Differentiated HepaRG® cells adhered to NANOSTACKS™ and maintained their viability for 9 days of cell culture

  • HepaRG® cells were metabolically active, as CYP3A4 was detected across all timepoints

  • HepaRG® cells can successfully be incorporated into NANOSTACKS™

Liver-Brain Axis Model

  • HepaRG® were successfully cocultured with neural cell lines SH-SY5Y and U-138 MG, recapitulating the liver-brain axis

  • The triculture IC50 was 26.8% lower than the monoculture, suggesting that the liver component increased the model's sensitivity

  • Demonstrates feasibility for drug testing and studying liver-brain crosstalk in physiological and pathological conditions

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