Product

HepatoPearl

Till now available 3D cellular models are not explored to their full potential. Cyprio’s solution, HepatoPearl, is a liver 3D cellular model that is easy to handle, adaptable to any bioassay and any established experimental pipeline. HepatoPearl can provide precise answers to drug assays such as long term DPMK, DILI and drug efficacy.
HepatoPearl is a physiologically relevant 3D in vitro model of Primary Human Hepatocytes (PHH) fabricated using the BioPearl technology. HepatoPearls are produced using cryopreserved and freshly isolated PHH. They have been characterized and validated by our research team using different donor cells.
Key Features of HepatoPearls include:

High predictability

and robustness for diverse drug screening assays

Long-term viability

of 45 days with high and stable metabolic function

Native tissue-like

polarization and cell-cell contacts

Easy manipulation

and integration to established laboratory workflows

Size-controlled Spheroid

generated per capsule

Miniaturization

≈150 cells per capsule

Customizability

possibility of customizing cell number per well depending on the type of readout and the corresponding signal detection threshold

Easy visualization

and possibility to remove alginate if needed

Spheroid formation - Cyprio
Spheroid formation
During the 7 days post encapsulation, cells self-assemble to form a compact micrometric spheroid within each capsule. Homogenous oxygen and nutrient diffusion supports cell physiology within the HepatoPearls over long periods.
Native tissue-like cellular organization and polarization
HepatoPearls effectively mimic the in vivo-like complex 3D architecture of the liver. Cell polarization, tight junctions and bile canaliculi network presence are some of the major aspects present in HepatoPearls, which impacts their physiological relevance as an in vitro model. Presence of tight junction protein, ZO-1 as well as cytoskeleton protein, F-actin, in the HepatoPearls indicates the analogy of this in vitro model to the native tissue.
Native tissue-like cellular organization and polarization - Cyprio
Native tissue-like cellular organization and polarization - Cyprio
Native tissue-like cellular organization and polarization - Cyprio
Viability - Cyprio
Viability
HepatoPearls are viable during 6 weeks and maintain their morphological structure and physiological characteristics all along this period. Besides, transparency of alginate allows real-time microscopic screening of cell behavior in HepatoPearls.
Long term liver-specific function
HepatoPearls maintain a relatively high and stable liver-specific functions namely albumin synthesis and urea secretion for over 38 days.
Graphic Long term liver-specific function - Cyprio
Graphic Long term liver-specific function - Cyprio
Relative quantification of gene expression compared to HepatoPearls at day 1 - Cyprio
CYP activity fold induction normalized to samples treated with DMSO 0,3% - Cyprio
Extended maintenance of metabolic activity
HepatoPearls maintain a high metabolic level over 5 weeks: major Cytochrome P450 enzymes, phase II metabolizing enzymes and nuclear receptors.
Moreover, long-term CYP P450 cytochromes inducibility of HepatoPearls is validated with three reference inducer molecules (omeprazole, phenobarbital, and rifampicin) and their three target enzymes (CYP1A2, CYP2B6, and CYP3A4).
Putting all together, HepatoPearls provide a relatively large working window for long experiments such as prediction of hepatic clearance over long incubations with low-clearance compounds, toxicokinetics with chronic drug exposure and high content screening through imaging.