HepatoPac is an in vitro liver model designed for both short and long-term ADME, toxicology and efficacy studies during pre-clinical drug discovery. Its proprietary patterning of hepatocyte "islands" with supportive stromal cells replicates the physiological microenvironment of the liver, promoting hepatocyte health and enabling stable metabolic activity for over four weeks.
HepatoPac technology was invented by Howard Hughes Medical Institute Investigator, Sangeeta Bhatia, at MIT, and is centered on the concept that "architecture is important." Cryopreserved primary hepatocytes from a species-of-interest (human, rat, monkey or dog) are micropatterned within industry-standard microwell plates creating hepatocyte islands which are surrounded by supportive stromal cells. This proprietary architecture is the key to HepatoPac's longevity and superior predictive power.
Key HepatoPac Features:
- Long-term Stability and Functionality (> 4 weeks)
- Extensively Characterized & Validated
- Multi-species Platform
- Superior Predictive Power Over Other Models
- High Throughput Format
Hepatocyte health, functionality and liver enzyme activity are extensively characterized for each donor. Shown below are examples of typical HepatoPac validation. Results for individual donors are available in Specification Sheets.
Liver Function Read-out
HepatoPac Co-cultures remain viable and highly functional for 4 weeks in culture, unlike alternative model systems such as primary hepatocyte suspensions which lose functionality (i.e. albumin and urea secretion) within several hours to a few days.
Maintenance of Phase I CYP Activity & Phase II Enzymes
Type Title Application Note HepatoPac® A Bioengineered Micro-Liver Platform for Predictive Drug Metabolism and Toxicity Studies. A Predictive, In Vitro Micro-Liver Co-culture System Providing In Vivo Performance Publication A Micropatterned Hepatocyte Coculture Model for Assessment of Liver Toxicity Using High-Content Imaging Analysis. Assay Drug Dev Technol., Vol. 12 (1), p 16-27, (2014). Publication Bridging in vitro and in vivo metabolism and transport of faldaprevir in humans using a novel cocultured human hepatocyte system, HepatoPac®. Drug Metab and Dispos. Early Access. December 2013. Publication Meeting the challenge of predicting hepatic clearance of compounds slowly metabolized by cytochrome P450 using a novel hepatocyte model, HepatoPac® Drug Metab and Dispos. Vol. 41(12), p 2024-2032 (2013). Publication Bioactivation and Toxicity of Acetaminophen in a Rat Hepatocyte Micropatterned Coculture System. Journal of Biochemical and Molecular Toxicology. Early Release Epub, August 5, 2013. Publication Long-Term Stability of Primary Rat Hepatocytes in Micropatterned Co-Cultures. Journal of Biochemical and Molecular Toxicology, Vol. 27(3), p 204-212 (2013). Publication The Use of Micropatterned Co-Cultures to Detect Compounds that Cause Drug induced Liver Injury in Humans. Toxicol. Sci. 132 (1): p 107-117, (2013). Publication Assessment of MicroPatterned Hepatocyte Co-culture System to Generate Metabolites. Drug Metabolism and Disposition, Vol. 38(10), p 1900-1905 (2010). Poster Microscale culture of human liver cells for drug development. Nat Biotechnol, 26(1), 120-126 (2007).