HEPATOPAC Technology is used to create stable in vitro liver models that enable long-term hepatic metabolism and toxicity studies. HEPATOPAC cultures, formed using a proprietary patterning method, consist of hepatocyte “islands” surrounded with supportive stromal cells. This specialized architecture replicates the physiological microenvironment of the liver. Hepatocytes remain healthy and viable in the HEPATOPAC platform and demonstrate physiologically-relevant transporter function and phase I and phase II metabolic activity for over four weeks. HEPATOPAC models show better in-vitro in-vivo correlations (IVIVC) than conventional hepatocyte models, especially for medium- and low-turnover compounds.
Features of HEPATOPAC cultures include:
- Long-term stability and functionality (>4 weeks)
- Primary hepatocytes that are extensively characterized and validated
- Multi-species platform (Human, Rat, Dog, Monkey)
- High-throughput format
Products and Services Using HEPATOPAC Technology
HEPATOPAC technology is available in ready-to-use HEPATOPAC kits using primary hepatocytes for the following species:
The kits are designed for both short and long-term ADME, toxicology, and preclinical efficacy studies.
Additionally, BioIVT provides a comprehensive portfolio of hepatic ADME Tox research services using HEPATOPAC cultures as well other hepatocyte models. We work with our clients to design and implement research programs to answer all of their liver-related questions and achieve their product development objectives.
HEPATOPAC Architecture: Micropatterned Hepatocyte Co-cultures
HEPATOPAC cultures have a unique specialized architecture and an optimal ratio of hepatocyte islands to stromal cells. This gives the hepatocyte co-cultures greater longevity and stable metabolic activity compared with other in vitro models. The process to create a HEPATOPAC culture starts by selecting primary hepatocytes from a species of interest. The cells are then micropatterned on industry standard plates creating the islands; stromal cells are added, forming a culture. This precise cytoarchitecture supports consistent cell-to-cell interactions leading to reproducible experimental results and improved prediction of in vivo effects.
The architectural organization of HEPATOPAC cultures has been empirically optimized to promote hepatocyte vitality and enable stable metabolic activity for weeks, rather than hours or days, the typical duration of other culture systems.
HEPATOPAC Co-cultures Mimic the Liver
In the liver, polarized hepatocytes are in direct contact with the blood supply and the bile canaliculi, and are arranged in hepatic plates that are only one to two cells thick. The micropatterned design of HEPATOPAC cultures simulates this microscale in vivo architecture within the wells of industry-standard microtiter plates, thereby creating a model of fully functional hepatic plates.
Micropatterning of primary hepatocyte co-cultures, in contrast to random co-culture, promotes and stabilizes metabolic activity. Hepatocyte-stromal coupling is known to promote cellular health. But more than that, the dimensions of the hepatocyte islands and the optimal ratio of the hepatocytes to stromal cells is what sets HEPATOPAC products apart from suspension, plated, sandwich-culture, random co-cultures and other hepatocyte models.
HEPATOPAC cultures demonstrate metabolic activity that reflects physiologically-relevant levels of all Phase 1 and 2 metabolizing enzymes, transporter proteins, and in vivo-matched physiologic function.
As shown in the diagram below, HEPATOPAC co-cultures are micropatterned so that individual hepatocyte islands are 500 µm in diameter, are 1200 µm from island center to center and are at 60° angles relative to adjacent islands. This configuration has been demonstrated to be ideal for the long-term viability of the culture.