Hepatocytes are specialized liver cells that perform many metabolic, endocrine and secretory functions. They also serve as the primary site for drug metabolism, uptake and clearance in the liver. The liver receives a unique blood supply: a simultaneous mixture of oxygenated and deoxygenated arterial blood entering from the aorta and partially deoxygenated but nutrient-rich venous blood entering the portal vein.
They Are The Gold Standard For Metabolism And Drug-Drug Interaction Assays.
Hepatocytes are the central cells of the liver and perform all major hepatic functions. Primary hepatocytes are the gold standard for metabolism and drug-drug interaction (DDI) assays. Hepatocytes have become essential for many metabolic and DDI assays that evaluate chemical entities’ stability, metabolism, and toxicity (Chemical Entities or NCEs). These assays include metabolite profiling, P450 inhibition, P450 induction, and transporter activity.
They Are A Convenient And Cost-Effective Alternative To In Vivo Testing.
Hepatocytes are multifunctional cells that play a key role in metabolic processes, such as protein synthesis and storage, carbohydrate metabolism, lipid metabolism, and detoxification. These cells are a critical part of human health and a valuable tool for drug development. Hepatic hepatocytes and non-parenchymal cells (NPCs) are often used in toxicity research because they recapitulate the liver’s complex structure and function. They also help to identify hepatotoxicity cues. Primary hepatocytes are a convenient and cost-effective alternative to in vivo testing for toxicity screening because they express the entire complement of hepatic drug-metabolizing enzymes and transporters. However, they are prone to cellular deterioration and dedifferentiation over long-term culture periods.
They Are A Convenient And Cost-Effective Alternative To Cell Lines.
When compared to cell lines, primary hepatocytes offer many advantages. They are readily available, scalable and cost-effective. They can be purchased as pre-plated cryopreserved fresh hepatocytes or in a plateable suspension format for extended incubations, relay studies and drug-drug interaction assays. In addition to being readily available and scalable, primary hepatocytes are the gold standard for metabolism and drug-drug interaction assays. They are also the preferred method for hepatocyte transplantation to regenerate liver tissue in animal models of liver disease. They can be expanded efficiently and over multiple passages, and they maintain their hepatic-like functionality in vivo after transplantation into mice.
They Are A Convenient And Cost-Effective Alternative To Animal Models.
Unlike cell lines and animal models, primary hepatocytes maintain their original structure and function in vitro and are a suitable model for evaluating drug metabolism and toxicity. They are widely accepted as the gold standard for hepatocyte-based drug-metabolizing enzyme and transporter activity studies. Primary hepatocytes can be sourced in plateable or suspension formats and are available for many common in vitro assays. They are a convenient and cost-effective alternative to animal models. Primary hepatocytes are a convenient and cost-effective alternative to human models for metabolism, drug-drug interaction (DDI), drug transporter activity, and drug toxicity testing. These cells are well-suited for in vitro testing because they are highly biotransformative and have abundant hepatocyte enzymes essential for a wide range of assays.
They Are A Way To Develop A New Cultural System.
Despite decades of research and development, the proliferation of viable and functional primary human hepatocytes remains a significant challenge in cell therapies and liver tissue engineering. Various in vitro systems, including collagen or matrigel sandwich cultures, co-cultures with stromal cells and 3D aggregate cultures, can maintain liver function for a short time after seeding. Still, they do not mimic the multi-cellular liver environment and are prone to contamination and batch-to-batch differences in ECM substrates. To address these limitations, we developed a new culture system that combines low attachment plates and collagen gel. Hepatocyte spheroids from this system maintain hepatic function and exhibit morphological and functional properties for up to 5 weeks in hanging drop culture conditions.
They Are A Convenient And Cost-Effective Alternative To Hepatic Spheroids.
In addition to their hepatocyte-specific functions, primary hepatocytes are widely accepted as the gold standard for metabolic and drug-drug interaction assays. Their high clearance1 makes them an excellent tool for testing the effects of drugs on liver metabolism and hepatocyte function. However, there are significant lot-to-lot differences in how long primary hepatocytes stay viable and retain functionality over time in culture, which can limit their application. This is especially true when the cells are overlaid with ECM or other cellular components or co-cultured with stromal cells.
To address these issues, we have developed a 3D PHH spheroid system that maintains hepatocyte-specific morphology and viability for at least five weeks in serum-free, chemically defined conditions. This provides an easily scalable in vitro platform to study hepatocyte-specific genotypes of interest, inter-individual variability, and drug response mechanisms and to evaluate the impact of a wide range of compounds. Hepatocytes are a critical cell type that performs all major liver functions, including protein synthesis and storage, carbohydrate metabolism and detoxification. They also play a role in hepatocyte regeneration. Over the past two decades, the challenge of prolonged culture and proliferation of viable and functional primary hepatocytes has been paramount for hepatocyte-based cell therapy and liver tissue engineering applications.
