Sekisui XenoTech has just been issued U.S. Patent No. 9,642,355 for the “cryopreservation of cells and subcellular fractions,” specifically related to Sekisui XenoTech’s CryostaX® test systems. This hepatocyte cryopreservation method was invented by Maciej Czerwinski, Ph.D., Director of Consulting for Sekisui XenoTech. [Read more…]
XenoTech’s pre-lysate tissue sample BioBank for liver research
Sekisui Xenotech’s Liver Research BioBank is committed to providing high-quality but affordable diseased & normal pre-lysate tissues for research applications. These tissues are collected with the initial intent for transplant, making this Liver Biobank an ideal tool for advanced basic medical research and new drug developments.
NADPH RapidStart regeneration system for long-term metabolism
NADPH is a critical cofactor supporting numerous biochemical reactions. In ADME-Tox studies, NAD(P)H regeneration is strongly recommended when using drug metabolizing enzymes (ex. Cytochrome P450 (CYP), Flavin-containing MonoOxygenases (FMO)), Recombinant CYPs (incl. bactosomes) or cellular fractions (Microsomes, S9). Currently, the most simple and cost-effective way to regenerate the NAD(P)H in situ and enzymatically is to use the commercially-available RapidStart™ NADPH Regenerating System (Xenotech-Sekisui). [Read more…]
Comparison of XenoTech Hepatocytes to HepaRG® Cell Line
Oral drugs typically require effective half lives in the region of 10 – 20 h for once or twice daily dosing. For candidate drugs with low distribution volumes it’s necessary to define intrinsic clearance (CLint) values of 0.1 – 1µL/min/million human hepatocytes (Grime et al., 2013). Svanberg & co-workers wanted to compare in vitro systems that potentially can provide a solution to the problem of robustly defining low CLint values in human hepatocytes. Recently the HepatoPac™ Platform and a novel relay suspension method (Di et al., 2012) have shown promising results producing reliable low CLint values. XenoTech have made a well characterised platable pool of cryopreserved human hepatocytes (5 donors) commercially available (CryostaX+), which makes plated hepatocyte methods attractive to evaluate. Also of interest is the HepaRG® human hepatoma cell line, since it offers stable expression of drug metabolising enzymes (DMEs) (Kanebratt et al., 2008, Aninat et al., 2006).
The authors evaluate all four methods but this poster focuses on HepaRG & plated primary hepatocytes, since data from Hepatopac and Relay at present are inconclusive.
“Determination of Low Intrinsic Clearance Values using Primary Human Hepatocytes and the HepaRG® Cell Line – A Comparison of Methods”
Svanberg, et al – AstraZeneca R&D
Contact jean-francois.tetu @ tebu-bio.com to get your own copy of this poster.
Plateable Hepatocytes… the "one cell type doesn't fit all" syndrome
Hepatocytes are commonly used in drug discovery and preclinical drug development to perform experiments requiring intact cellular systems. Intact hepatocytes contain the major hepatic drug-metabolizing enzymes required to study the four categories of xenobiotic biotransformation: Hydrolysis, Reduction, Oxidation and Conjugation. Because of these enzymes, hepatocytes provide a viable and cost-effective alternative to in vivo compound testings.
6 tips for thawing hepatocytes
Cryopreserved hepatocytes contain the major hepatic drug-metabolizing enzymes required to study the four categories of xenobiotic biotransformation: hydrolysis, reduction, oxidation and conjugation. Cryopreserved hepatocytes are ready when you are. A simply quick-thaw protocol is performed to remove cryoprotectant and have viable cells… However, the functionality and the viability of these cells can be impaired by an incorrect thawing procedure… [Read more…]
Maximise availability & reduce variability in hepatocytes studies
Pooled human hepatocytes are a preferred test system in many drug discovery and development applications which require intact cellular systems for in vitro testing. Intact hepatocytes contain the major hepatic drug-metabolizing enzymes and co-factors required to evaluate the metabolism and potential drug-drug interactions of drug candidates effectively.
Over the last decade, improvements of cryopreservation technologies make possible using cryopreserved human hepatocyte more conveniently. Pooled cryopreserved hepatocytes reduce the inter-individual differences and polymorphic distribution of liver enzymes. However, this is crucial to carefully select a pool according to its performance but also the application used for. [Read more…]
Activation & de-activation pathways of hepatic fibrosis
Liver fibrosis is the result of an imbalance between production and dissolution of extracellular matrix. It has been described that Stellate cells, liver myofibroblasts, and bone marrow derived cells converge in a complex interaction with hepatocytes and immune cells to induce response to liver injury.
in vitro exploration of hepatobiliary drug disposition
What is an integrated hepatic model and why is it important?
An integrated in vitro model maintains physiologic cellular components and processes at in vivo-relevant amounts. In the sandwich-cultured hepatocyte model, relevant drug transporter proteins (uptake and efflux), as well as drug metabolizing enzymes (Phase I and II), are expressed, maintained, and functioning together in the same system. The figure below graphically represents this concept (picture from Qualyst Transporter Solutions). [Read more…]