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You are here: Home / Archives for Hepatocytes

What to do with Microsome Stable, Low-Turnover Compounds

09/04/2018 By Isabelle Nobiron Leave a Comment

In a few forthcoming posts, I’d like to share several short articles published by Dr Chris Bohl of Sekisui Xenotech, a technical expert in the field of ADME-Tox tools and applications. I feel they may be of special interest to researchers working in the field of ADME-Tox studies.

Today, we’ll take a look at compounds that exhibit high metabolic stability in hepatocytes and subcellular fractions (S9, microsomes and cytosol), as these can be a challenge for ADME scientists. [Read more…]

Filed Under: ADME-Tox Tagged With: ADME-Tox studies, Hepatocytes

Liver tissue BioBank: High quality specimens for liver disease research

09/04/2018 By Isabelle Nobiron Leave a Comment

Sekisui Xenotech’s Research BioBank provides you with normal and diseased human liver tissue samples for scientific investigation. Tissues are collected with the initial intent for transplant, thus making them perfect candidates to advance basic medical science and contribute to the development of new treatments.

The care taken to preserve viability of the tissue intended for transplantation distinguishes these Research Biobank specimens from samples collected at a typical post-mortem, usually compromised by several hours of a warm ischemia. So what are the other benefits of the biobank? [Read more…]

Filed Under: ADME-Tox Tagged With: DILI, Hepatocytes, liver diseases, liver injuries

Hepatocytes: large donor pool for your DMPK applications with Hepatosure®

17/10/2017 By Isabelle Nobiron Leave a Comment

HepatoSure® is a pool of human hepatocytes designed to facilitate your DMPK applications with a consistent hepatocyte product over time (years). HepatoSure® is best suited for both discovery and development of ADME-Tox study assays where generation and comparison of data is required. Let’s take a closer look, and you might like to benefit from our current offer to try these for yourself (see below). [Read more…]

Filed Under: ADME-Tox Tagged With: ADME-Tox, Hepatocytes

Sekisui XenoTech Awarded Cryopreservation Patent for Cryostax single freeze hepatocytes

12/05/2017 By Isabelle Nobiron Leave a Comment

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…]

Filed Under: News Tagged With: Cryostax, Hepatocytes, Platable hepatocytes, Xenotech

NADPH RapidStart regeneration system for long-term metabolism

04/04/2016 By Jean-François Têtu, PhD Leave a Comment

RapidStart stabilityNADPH 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…]

Filed Under: ADME-Tox Tagged With: CYP, Drug enzymes, Hepatocytes, metabolism, Microsomes, NADPH regeneration

Comparison of XenoTech Hepatocytes to HepaRG® Cell Line

06/11/2014 By Jean-François Têtu, PhD Leave a Comment

Metabolite formation for Diclofenac (2C9) and Midazolam (3A4) in XenoTech tebu-bio Cryostax pool of 5Oral 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.

Filed Under: News Tagged With: ADME, Hepatocytes, Platable hepatocytes

Plateable Hepatocytes… the "one cell type doesn't fit all" syndrome

27/06/2014 By Jean-François Têtu, PhD Leave a Comment

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.

[Read more…]

Filed Under: ADME-Tox, Cell Sourcing - Cell Culture Technologies, Drug Discovery Tagged With: ADME, Drug discovery, Fresh hepatocytes, Hepatocytes, Individual donors, Platable hepatocytes, Toxicology, Transpoters

6 tips for thawing hepatocytes

05/05/2014 By Jean-François Têtu, PhD Leave a Comment

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…]

Filed Under: ADME-Tox, Cell Sourcing - Cell Culture Technologies, Headlines, Supplying Discovery Tools Tagged With: ADME, Hepatocytes, Liver, Primary cells, Thawing procedure, Tips & tricks

Maximise availability & reduce variability in hepatocytes studies

02/05/2014 By Jean-François Têtu, PhD Leave a Comment

ADMEPooled 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…]

Filed Under: ADME-Tox, Cell Sourcing - Cell Culture Technologies, Headlines, Supplying Discovery Tools Tagged With: ADME, Aldehyde oxidase, Hepatocytes

Activation & de-activation pathways of hepatic fibrosis

15/04/2014 By Jean-François Têtu, PhD Leave a Comment

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.

[Read more…]

Filed Under: ADME-Tox, Cell Sourcing - Cell Culture Technologies, Supplying Discovery Tools Tagged With: Fibrosis, Hepatocytes, Liver

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