Architecture is Important

HepatoPac® co-cultures are different from sandwich cultures and regular or "random" co-cultures.  They contain proprietary patterning of primary hepatocyte "islands" in a "sea" of stromal cells which replicates the physiological microenvironment of the liver. The architectural organization of HepatoPac co-cultures has been empirically optimized to promote hepatocyte health and enable stable metabolic activity for weeks, rather than hours or days.

HepatoPac hepatocyte islands surrounded by stromal cells for optimal function
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How does HepatoPac 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 co-cultures was designed specifically to simulate 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, rather than simple random co-cultures, promotes and stabilizes physiologically relevant metabolic activity. Hepatocyte-stromal coupling is known to promote cellular health, but more than that, the optimal ratio and dimensions of hepatocyte islands to stromal cells is what sets HepatoPac products apart from the competition. Metabolic activity reflective of physiologically relevant levels of all Phase 1 and 2 metabolizing enzymes, transporter proteins, and in vivo-matched physiologic function comprise a platform that provides the most accurate data in the industry for all applications1,2.

HepatoPac's micropatterned architecture is patented and promotes ideal homotypic and heterotypic interactions between stromal cells and hepatocytes.
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Various cellular patterns were assessed to determine optimum heterotypic interactions and co-culture stability.  Current HepatoPac products 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. Morphology of HepatoPac and random co-cultures (10x) are shown.

Differing diameters and spacing of HepatoPac islands show different levels of albumin and urea production.
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Primary hepatocytes islands within HepatoPac co-cultures were micropatterned at a specified island size (30 to 4800µm diameter) and center-to-center spacing (no spacing versus 90 to 1200µm apart).  Random co-cultures of primary hepatocytes and supportive stromal cells were also established.  Albumin and urea secretion were measured.  

  1. Microscale Culture of Human Liver Cells for Drug Development. Nat Biotechnol. Vol. 26(1), p. 120-126 (2008).
  2. Assessment of MicroPatterned Hepatocyte Co-culture System to Generate Metabolites. Drug Metabolism and Disposition, Vol. 38(10), p 1900-1905 (2010).
Technical Resources
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 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 Microscale culture of human liver cells for drug development. Nat Biotechnol, 26(1), 120-126 (2007).
Publication Assessment of MicroPatterned Hepatocyte Co-culture System to Generate Metabolites. Drug Metabolism and Disposition, Vol. 38(10), p 1900-1905 (2010).
Publication Controlling Cell Interactions by Micropatterning in Co-Cultures: Hepatocytes and 3T3 Fibroblasts. Journal of Biomedical Materials Research, Vol. 34, 189-199 (1997).
Poster Assessment of Rat and Human HepatoPac® to Detect Compounds that Cause Drug Induced Liver Injury in Humans