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Updated: Jun 23, 2025
A Biomimetic Model for Liver Cancer to Study Tumor-Stroma Interactions in a 3D Environment with Tunable Bio-Physical Properties
Published on: August 7, 2020
Advanced three-dimensional in vitro liver models to study the activity of anticancer drugs
Agnieszka Zuchowska1, Sonia Frojdenfal1, Maciej Trzaskowski2
1Faculty of Chemistry, Warsaw University of Technology, Warszawa, Poland.
Abstract:
The liver is one of the most important organs in the human body. It performs many important functions, including being responsible for the metabolism of most drugs, which is often associated with its drug-induced damage. Currently, there are no ideal pharmacological models that would allow the evaluation of the effect of newly tested drugs on the liver in preclinical studies. Moreover, the influence of hepatic metabolism on the effectiveness of the tested drugs is rarely evaluated. Therefore, in this work we present an advanced model of the liver, which reflects most of the morphologically and metabolically important features of the liver in vivo, namely: three-dimensionality, cellular composition, presence of extracellular matrix, distribution of individual cell types in the structure of the liver model, high urea and albumin synthesis efficiency, high cytochrome p450 activity. In addition, the work, based on the example of commonly used anticancer drugs, shows how important it is to take into account hepatic metabolism in the effective assessment of their impact on the target organ, in this case cancer. In our research, we have shown that the most similar to liver in vivo are 3D cellular aggregates composed of three important liver cells, namely hepatocytes (HepG2), hepatic stellate cells (HSCs), and hepatic sinusoidal endothelial cells (HSECs). Moreover, we showed that the cells in 3D aggregate structure need time (cell-cell interactions) to improve proper liver characteristic. The triculture model additionally showed the greatest ability to metabolize selected anticancer drugs.
Insights
Researchers developed an advanced 3D liver model using hepatocytes, stellate cells, and endothelial cells. This model accurately mimics liver metabolism, crucial for evaluating drug efficacy and toxicity in preclinical studies.
Area of Science:
- Hepatology and Drug Metabolism
- Biomedical Engineering
- Preclinical Pharmacology
Background:
- The liver is vital for drug metabolism, but current preclinical models lack accuracy in reflecting in vivo conditions.
- Drug-induced liver damage and the impact of hepatic metabolism on drug effectiveness are poorly evaluated.
- There is a need for advanced liver models that replicate in vivo morphology and metabolic functions.
Purpose of the Study:
- To develop and validate an advanced 3D liver model for preclinical drug evaluation.
- To assess the importance of hepatic metabolism in evaluating drug impact, using anticancer drugs as an example.
- To demonstrate the metabolic capabilities of the developed liver model.
Main Methods:
- Constructed a 3D cellular aggregate liver model using hepatocytes (HepG2), hepatic stellate cells (HSCs), and hepatic sinusoidal endothelial cells (HSECs).
- Cultured cells in 3D aggregates to allow for cell-cell interactions and development of liver-like characteristics.
- Assessed the model's morphological and metabolic features, including urea and albumin synthesis and cytochrome P450 activity.
- Evaluated the metabolic capacity of the triculture model using common anticancer drugs.
Main Results:
- The 3D triculture model, comprising HepG2, HSCs, and HSECs, closely resembles the in vivo liver structure and function.
- Cell-cell interactions within the 3D aggregate are essential for developing proper liver characteristics over time.
- The model demonstrated high efficiency in urea and albumin synthesis and significant cytochrome P450 activity.
- The triculture model exhibited the greatest ability to metabolize selected anticancer drugs, highlighting the importance of hepatic metabolism assessment.
Conclusions:
- A 3D triculture liver model using HepG2, HSCs, and HSECs provides a robust platform for preclinical drug testing.
- This advanced model accurately reflects in vivo liver morphology and metabolic functions, including drug metabolism.
- Incorporating hepatic metabolism assessment using this model is critical for effective drug evaluation and understanding drug-induced liver damage.
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