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…]
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…]
Hepatic stellate cells (HSC, also known as perisinusoidal cells or Ito cells), are liver-specific mesenchymal cells found in the space of Disse. HSC maintain interactions with sinusoidal endothelial cells and hepatic epithelial cells. The stellate cells are involved in liver physiology and fibrogenesis (formation of scar tissue in response to liver damage). [Read more…]
An interesting poster has recently been published by XenoTech: “Selection of Human Liver S9 and Cytosol Fractions for Evaluating Clearance by Aldehyde Oxidase (AO): The Impact of Low Versus High AO Activity Lots” by Phyllis Yerino, Clayton Otwell, Zell Woodworth and David B Buckley (XenoTech, LLC, Lenexa, KS, USA). [Read more…]
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…]