3D InSight™ Rat Liver Microtissues

Primary Sprague-Dawley hepatocyte-derived 3D rat liver models delivering greater physiological relevance for investigative toxicology studies

3D InSight™ Rat Liver Microtissues
  • Leverage scaffold-free 3D microtissue models composed of primary rat hepatocytes and NPCs
  • Predict drug-induced liver injury (DILI) in a 3D in vitro rat model that reflects in vivo species-specific toxicities (e.g., sensitivity to Acetaminophen)
  • Peform mechanistic toxicity studies in an advanced model featuring intact hepatocyte function, bile salt excretion, and inflammatory-mediated toxicity pathways

 

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  • InSphero 3D InSight™ Rat Liver Microtissues are produced and shipped to customers in the United States and Europe. Place your order on Tuesday at 6 PM (CET) three weeks before your desired ship date based on our production schedule. (Please indicate your desired ship date when requesting a quote.) For more detailed information about the order and shipment dates for all InSphero microtissue products, please see our quarterly production schedule.

    3D InSight™ Rat Liver Microtissues
    Production lead time: please inquire

    Catalog # Description
    MT-02-001-01 3D InSight™ Rat Liver Microtissues from primary hepatocytes, monoculture (96x)
    MT-02-001-04 3D InSight™ Rat Liver Microtissues from primary hepatocytes, co-culture with NPCs (96x)
    CS-07-002 Maintenance Medium for Rat liver 500 mL*
    AK-01-001-01 Cytotoxicity Assay Kit (for up to 4 96-well plates)

    For volume discounts (starting at 2 plates) and shipping cost, please contact our sales staff to request a quote. We start rat liver microtissue production runs every three weeks, special formulations upon request.

    *only available together with 3D InSight™ Microtissues

  • Organotypic microtissue composition

    3D InSight™ Rat Liver Microtissues are generated using scaffold-free hanging drop co-culture of freshly isolated primary rat hepatocytes and non-parenchymal cells (NPCs) in a ratio designed to reflect the organotypic cell composition of native rat liver. Hepatocytes are polarized and form functional bile-canaliculi. In addition, Kupffer cells are incorporated in the microtissue and display sensitivity to external stimuli, such as bacteria-derived lipopolysaccharide (LPS). The presence of stellate cells helps maintain hepatocyte functionality. No bioartificial scaffold materials are used in the microtissue production process. InSphero 3D InSight™ Rat Liver Microtissues are delivered in GravityTRAP™ plates, ready to use in experiments within hours of receipt in your lab.

                                             3D organotypic rat liver microtissue models

     

    Figure 1: Rat Liver Microtissues were stained for glycogen storage (Periodic Acid-Schiff, PAS), and presence of Kupffer cells (CD68 marker) and stellate cells (αSMA marker). Extensive storage of glycogen indicates high metabolic activity, CD68 staining shows incorporation of Kupffer cells in microtissues, and peripheral αSMA staining indicates the presence of stellate cells.

  • High functionality

    InSphero's proprietary 3D Select™ Process ensures an abundance of tight cell-cell contacts during microtissue formation. Thus, hepatocytes remain polarized, differentiated, and active. 3D InSight™ Rat Liver Microtissues display viability of up to 28 days in culture, enabling chronic toxicity testing with repeat-dose, long-term drug exposure. The model is capable of de novo synthesis of bile acids, and an intact bile canaliculi network ensures proper clearance of bile acids into the medium.


    Viability and functionality of 3D  Rat Liver Microtissue models

    Figure 1: Viability and functionality of 3D InSight™ Rat Liver Microtissues over 3 weeks in culture. The stable ATP content indicates viability over the whole culture period, as well as hepatocyte functionality as measured by albumin secretion.

  • DILI testing

    Hepatic injury remains one of the most common causes of drug attrition during the post-marketing phase of drug development. 3D microtissue models are perfectly suited for early assessment of potential drug induced liver injury (DILI) during development of novel drugs, as they recapitulate major toxicity pathways (mitochondrial activity, BSEP-mediated bile salt excretion, presence of inflammatory cells) and may be used in long-term substance exposure testing. InSphero has developed 3D liver microtissues from primary hepatocytes obtained from commonly used pre-clinical animal model species, (including rats, dogs and monkeys) to offer species-specific toxicity testing. Testing in more than one model system is important as some drugs, such as acetaminophen, display differential toxicity between species (McGill et al. Toxicol Appl Pharmacol 2012). Whereas acetaminophen shows only little toxicity in rats, humans are much more susceptible. This inter-species difference can be recapitulated between 3D InSight™ Human and Rat Liver Microtissues (see below). Human Liver Microtissues displayed 6-fold higher sensitivity towards acetaminophen than Rat Liver Microtissues, indicating the suitability of cross-species comparisons to determine species specific toxicity.



    Dose response curve of acetaminophen

    Figure 1: Dose-response curve of acetaminophen (APAP) following 72-hour exposure of Human and Rat Liver Microtissues, followed by cell viability (CellTiter-Glo®, Promega Corp.) endpoint. 3D InSight™ Human Liver Microtissues exhibit an APAP IC50 value of 2 mM, whereas Rat Liver Microtissues display a 6-fold higher APAP IC50 value of 12 mM.

  • Applications

    3D InSight™ Rat Liver Microtissues are an excellent alternative to traditional animal models for:

    • Acute hepatotoxicity
    • Long-term hepatotoxicity
    • Species-specific toxicity testing
    • Mechanistic toxicity testing
      • Inflammation-mediated toxicity (idiosyncratic toxicity)
      • Mitochondrial toxicity
      • Oxidative stress
    • ADME/Tox

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