HepaRG cells are a specialized human liver cell line used in scientific research to study the liver’s functions and its response to various substances. Scientists use them to explore liver diseases and assess the effects of new drugs. In the laboratory, they provide a consistent model that mimics many aspects of human liver biology.
Defining HepaRG Cells: Origin and Key Properties
HepaRG cells originate from a human liver tumor from a patient with a chronic hepatitis C infection. Despite this cancerous origin, the cells can be guided in the laboratory to become cells that resemble normal, healthy liver cells. The cell line was developed in 2002 after researchers observed that a group of tumor cells could undergo complete hepatocyte differentiation.
These cells are progenitor cells, meaning they can develop into more specialized cell types. The primary characteristic of HepaRG cells is their capacity to differentiate into two distinct cell populations: hepatocyte-like cells and biliary epithelial-like cells. This is useful for creating a more complete picture of the liver’s structure. Hepatocytes are the primary cells of the liver, responsible for metabolic processes like breaking down drugs. Biliary epithelial cells line the bile ducts that transport bile. The ability to produce both of these cell types allows researchers to study their individual functions.
Another property of HepaRG cells is their stability as a cell line. They can be grown and multiplied over extended periods in culture while retaining their unique characteristics. This stability ensures that experiments produce consistent and reproducible results, which contrasts with other liver cell models that may lose their function quickly.
Applications of HepaRG Cells in Scientific Discovery
A primary application for HepaRG cells is in drug metabolism and pharmacokinetics, which examines how the body processes new medicines. Because differentiated HepaRG cells express drug-metabolizing enzymes, such as cytochrome P450s (CYPs), at levels comparable to human liver cells, they provide an accurate model to predict a drug’s metabolic fate.
Scientists also use HepaRG cells for toxicology studies to evaluate the potential for new drug candidates or environmental chemicals to cause liver damage. This is important for identifying drug-induced liver injury (DILI), a major reason for drug development failure. The cells can be used to screen for various forms of toxicity, including steatosis (fat accumulation) and cholestasis (bile flow disruption).
HepaRG cells serve as a platform for creating laboratory models of human liver diseases. Researchers have used them to study viral infections like hepatitis B and C, as the cells can be infected by these viruses and support their replication. This allows for investigation into the viral life cycle and the testing of new antiviral therapies. The cells are also used to model metabolic conditions like fatty liver disease.
Beyond these applications, HepaRG cells are employed in basic research to uncover the workings of liver physiology. They help scientists explore metabolic pathways, such as how the liver manages carbohydrates and lipids. This knowledge helps in understanding various liver-related health issues.
The Impact of HepaRG Cells on Liver Research
The availability of HepaRG cells has impacted liver research by addressing the limitations of other cell models. The traditional standard for in vitro liver studies has been primary human hepatocytes (PHHs), cells isolated from donor liver tissue. However, PHHs are scarce, their availability is unpredictable, and they exhibit variability between donors. PHHs also tend to rapidly lose their functions when cultured.
As an established cell line, HepaRG cells provide a reproducible supply of human liver cells, eliminating the donor-to-donor variability that can complicate study results. They maintain their functions, including high levels of metabolic enzyme activity, for up to four weeks in culture. This extended functional lifespan is longer than PHHs and allows for long-term experiments.
The human origin of HepaRG cells provides an advantage over animal models. The livers of animals can metabolize drugs and respond to toxins differently than human livers, so results from animal studies do not always predict human outcomes. By providing a human-specific system, HepaRG cells allow for more relevant assessments of drug safety and efficacy before clinical trials.
The ability of HepaRG cells to differentiate into both hepatocyte-like and biliary-like cells creates a more physiologically complete model compared to other immortalized cell lines, like HepG2, which have much lower metabolic activity. This co-culture system better reflects the cellular complexity of the human liver, enabling more comprehensive studies of drug transport and liver injury mechanisms. These advantages translate into more reliable data for drug development and a better understanding of human liver disease.