Cryopreserved Beagle Dog Hepatocytes

The liver fulfills many vital processes in mammals. It is the central organ of energy metabolism, responsible for the maintenance of the blood sugar level and the synthesis of plasma proteins under physiological and pathophysiological conditions.

Hepatocytes are the most prominent cells within the liver. Hepatocytes eliminate toxic substances from the blood. In this biotransformation process transporter proteins (influx and efflux transporter), phase I reactions (cytochrome P450 proteins), phase II reactions (mainly glucuronidation and sulfatation) play a central role.

Cryopreserved primary hepatocytes are perfectly suited for in vitro metabolism and toxicity / detoxification studies prior to preclinical or clinical tests.

Dog hepatocytes are isolated from livers obtained from male or female Beagle and are cryopreserved directly after isolation. Donor demographics stating vaccination status and health status of the animals are available for each animal. Cryopreserved Beagle hepatocytes are used in suspension assays and plated in 2D and 3D cell cultures.

PRIMACYT is one of the pioneers in the development of advanced in vitro model systems. We are a leading company in the field of research of human and animal hepatocytes. We offer fresh and cryopreserved animal hepatocytes in suspension and plated.

PRIMACYT is approved by the European Commission as an EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) and serves as member of the laboratory network responsible for the method validation.

Our colleagues are professionals and undergo continuous training in the preparation, isolation and cryopreservation of hepatocytes in general, including related co-products, methods and tools. We are a GLP certified laboratory since 2006.

In drug development, at least two in vivo repeated-dose toxicity studies of a drug candidate have to be performed in two different animal species before human studies can be initiated (https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm292340.pdf). In most cases these species are mouse or rat and dog or monkey.

Hepatotoxicity is a major cause for failure in drug development. For interpretation of hepatotoxicity data, it is important to understand potential interspecies differences in mechanisms that lead to drug toxicity. This includes
- drug uptake into the liver,
- biotransformation of the drug (Phase I and Phase II), and
- drug efflux from the liver

Interspecies differences in expression and activities in transport proteins and biotransformation enzymes may result in different intra- and extrahepatic concentrations of the drug.

Quantification of drug transporter protein by LC/MS has revealed significant interspecies differences in the expression of uptake and efflux transporters. On the other hand, in beagle hepatocytes expression of the two most important Organic Anion Transporters Oatp1a2 and Oatp1b4 (equivalent to human OATP1B1 and OATP1B3) was maintained at the same level as in dog liver tissue (Wang et al. 2014).

Wang L, Prasad B, Salphati L, Chu X, Gupta A, Hop C E.C.A., Evers R, and Unadkat J. D.: Interspecies Variability in Expression of Hepatobiliary Transporters across Human, Dog, Monkey, and Rat as Determined by Quantitative Proteomics, Drug Metab. Dispos., 2015, 43:367–374

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