Delivered ready-to-use in 96-well assay plates
Organotypic cell composition
3D InSight™ Human Liver Microtissues are generated by co-culture of primary human hepatocytes and non-parenchymal Kupffer cells to reflect the native cell composition of liver. To assure short delivery times and the availability of specific donor lots over months and years, InSphero has developed a unique production process based on cryopreserved hepatocytes. InSphero's expert-know-how in generation of 3D InSight™ Human Liver Microtissues guarantees excellent functionality, viability and reproducibility.
3D InSight™ Human Liver Microtissues are delivered as a ready-to-use model in standard 96-well format (GravityTRAP™). This format allows easy cultivation, observation and assaying of 3D InSight™ Human Liver Microtissues, without risk of losing microtissues over the culture time. InSphero's new liver model retains similar multiple endpoint compatibility as the currently used 2D culture formats but significantly enhances the predictive power of such assays.
Key product characteristics:
- Organotypic cell composition with primary human hepatocytes and Kupffer cells
- Culture life time of more than 5 weeks
- Superior liver-specific functionality as compared to 2D culture
- Liver cytoarchitecture is maintained including full expression of bile canaliculi
BSEP-staining of a InSphero 3D InSight™ Human Liver Microtissue showing polarized transporter protein expression and bile canaliculi.
Morphology of human liver microtissues
- Liver-like cytoarchitecture and stability is confirmed by H&E-staining over 28 days in culture
Hematoxylin and Eosin (H&E) stain of FFPE sections from 3D InSight™ Human Liver Microtissues cultivated over 4 weeks. Typical features of native human liver are apparent: cuboidal cell shape, polarization of hepatocytes and tight cellular interactions.
- Organotypic incorporation of Kupffer cells over 28 days in culture is shown by CD68-Immunohistochemistry
CD68-IHC of FFPE sections from 3D InSight™ Human Liver Microtissues cultivated over 4 weeks. Kupffer-cells are stained in deep brown. Kupffer cells remain incorporated over more than 4 weeks in culture.
- Polarized expression of bile salt export pump (BSEP) in 3D InSight™ Human Liver Microtissues is comparable to native human liver
BSEP-Immunohistochemistry staining of FFPE sections of healthy native human liver and 3D InSight™ Human Liver Microtissues. BSEP is stained in deep brown and is indicative of a functional bile-canalicular network.
Viability and functionality of human liver microtissues
- Viability of 3D InSight™ Human Liver Microtissues is maintained for more than 35 days in culture as shown by ATP-content
Intracellular measurement of ATP-content (CellTiter-Glo®, Promega) of 3D InSight™ Human Liver Microtissues over 5 weeks in culture (n=3). The ATP-content of 3D InSight™ Human Liver Microtissues stays stable over several weeks in culture.
- Hepatocyte specific functionality of 3D InSight™ Human Liver Microtissues for more than 35 days in culture as shown by albumin secretion
Quantification of albumin released into the supernatant by 3D InSight™ Human Liver Microtissues (Albumin ELISA, Bethyl-laboratories). The secretion rate is close to native human liver (approx. 3 pg/cell*h; from Meng, 2010, Expert Opin. Drug Metab. Toxicol.).
- Superior CYP3A4 enzyme activity of 3D InSight™ Human Liver Microtissues as compared to 2D cell culture
Measurement of CYP3A4-mediated midazolam hydroxylation of 3D InSight™ Human Liver Microtissues at culture day 7, 14, 21 and 28. The same hepatocyte lot was used for assessment of CYP3A4 activity in standard 2D-culture on day 2 after plating. The CYP3A4 enzyme increases over the culture period.
- «biased» discovery of MOA
Long term and chronic toxicity
Bile-acid transporter inhibition
- «unbiased» discovery of MOA
Liver disease modelling
Viral infections (e.g. HCR/HBV, AAV)
Toxicity mechanism Cellular indicator
Kupffer-cell function/toxicity IL-6 secretion
Mitochondrial impairment Mitochondrial activity Reactive metabolites Lower GSH content Metabolic competence Cytochrome activation/ induction Apoptosis Caspase 3/7 activation Steatosis, phospholipidosis Lipid accumulation Cholestasis Transporter proteins
Cancerogenicity DNA-synthesis Unbiased discovery of MOA Transcriptomics
Catalog # Description Price in USD MT-02-002-01 3D InSight™ Human Liver Microtissues from primary hepatocytes (96x) 2,158 MT-02-002-04 3D InSight™ Human Liver Microtissues from primary hepatocytes, co-culture with non-parenchymal cells (96x) 2,376 CS-07-001-01 3D InSight™ Human Liver Maintenance Medium - TOX (500 mL) 385* CS-07-001a-01 3D InSight™ Human Liver Maintenance Medium - AF (advanced formulation) 385* CS-07-001b-01 3D InSight™ Human Liver Maintenance Medium - INF (for inflammatory tox applications) 385* Related
AK-01-001-01 3D InSight™ Cytotoxicity Assay Kit 210
For volume discounts (starting at 2 plates) and shipping cost, please contact our sales staff to request a quote.
*only available together with 3D InSightTM Microtissues
Documents and downloadsProduct brochure
Webinar 3D liver models in toxicology basics
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