HµREL® “microliver” hepatic co-cultures
humanhepaticcocultureimagesheight298 HµREL®’s patent-pending, cell-based hepatic models are comprised of primary (i.e., actual) cryopreserved hepatocytes cultured together with cells of a non-parenchymal, stromal type. HµREL® developed this co-culture model in collaboration with the Center for Engineering in Medicine at The Massachusetts General Hospital, Boston (“CEM”). In prior decades CEM had invented a variety of earlier cell-based hepatic models, several of which remain in use today, including hepatocyte cultures that rely on the collagen gel overlay (“double gel”) method, and micropatterned hepatic co-cultures. While its predecessor were originally developed for use in academic research, the HµREL® cell-based models are the first that CEM deliberately engineered for use in industrial science, and that consequently are characterized by their manufacturability, industrial ruggedness,
convenience of use, and replicability, as well as by their high,
stable, and enduring responsiveness across numerous parameters of cellular function.

HµREL®’s high, stable and enduring cellular competency, which has been demonstrated to persist for weeks rather than for the hours or days typical of the most commonly utilized primary cell-based models, enables experimentation in domains not previously susceptible to in vitro methods, such as studies of clearance rates of slow-clearing compounds; studies of the time-based dynamics of primary, secondary, and tertiary metabolite generation; and repeat-dosing studies to probe for sub-acute or chronic toxicities; among others.
coculturesgraph HµRELhumanTM: formation of the 5-hydroxyomeprazole metabolite from omeprazole, mediated chiefly by CYP450 enzyme 2C19. As this chart exemplifies, the plateau of high, stable cellular competency starting around culture Day 6 is a typical characteristic of the HµREL® co-cultures, and has been demonstrated across multiple experimental endpoints using numerous test substrates. The three data series reflect results derived from three separate donor lots of primary cryopreserved human hepatocytes (data normalized to Day 1 results).

multi-readout, repeat-dose
DILI screening
DILI screening

Hurel microlivers afford better prediction than 3D

Toxicology Research
Long-enduring infectious liver disease platform
Toxicity Ratios*
A new marker for hepatotoxic chronicity

*patent pending
a new, patent-pending
efflux transport
assay method
Superior intrinsic clearance
and biotransformation of
low-turnover drugs