Human Liver NASH Model | InSphero

Test efficacy of anti-NASH drugs in an advanced 3D human liver disease model

The InSphero 3D InSight™ Human Liver NASH Model is a human liver microtissue designed for the study of mechanisms of non-alcoholic steatohepatitis (NASH) induction and in vitro screening of anti-NASH drug efficacy. The model includes all the critical liver cells and inducers needed to recapitulate the inflamed fatty liver disease state and serves as a powerful model for NASH drug discovery and development.

  • Rely on a physiologically relevant model composed of primary human hepatocytes (PHHs), hepatic stellate cells (HSCs), Kupffer cells, and liver endothelial cells (LECs)
  • Expand your assay window by leveraging a pre-qualified model that exhibits pro-inflammatory marker induction reflecting the in vivo disease state: MCP-1/CCL2, TNF-α, and MIP-1α/CCL3
  • Perform reproducible, throughput-compatible anti-fibrotic drug screening using a standardized, assay-ready 96-well model system, amenable to a host of certified application endpoints
human liver microtissue model before and after lipid loading to simulate NASH phenotype

The 3D InSight™ Human Liver NASH Model enables the study of liver NASH induction and inhibition of disease  progression. The screening-compatible Akura™ 96 microtissue format is well-suited for a wide range of assay endpoints and optimizes efficiency of microtissue handling processes.

3D InSight™ Human Liver NASH Model Characterization Data

Induction of NASH not only requires the presence of hepatocytes, in which large lipid vacuoles accumulate during steatosis, but also HSCs, which are activated by pro-inflammatory and pro-fibrotic stimuli. In addition, Kupffer cells (specialized macrophages located in the liver) and LECs influence the progression of inflammation and are thus required for a physiologically, mechanistically relevant in vitro model system. The 3D InSight™ Human Liver NASH model includes all these relevant primary liver cell types. Upon treatment with FFA, LPS and sugars, the model reflects increased lipid accumulation within hepatocytes, secretion of pro-inflammatory biomarkers, and deposition of fibrillar collagens. Treatment with Elafibranor, a PPARα/δ agonist under development by GenFit, resulted in decreased secretion of pro-inflammatory markers MCP-1/CCL2, TNF-α, and MIP-1α/CCL3. Concomitant treatment of FFA and LPS with an ALK5 inhibitor blocked HSC activation and collagen deposition, demonstrating suitability of the model system for testing anti-NASH compound efficacy.

Treatment with Elafibranor results in decreased inflammatory marker secretion in the 3D InSight™ NASH model
3D InSight™ Human liver NASH Model histological characterization data

Secretion of Inflammatory markers decrease with Elafibranor treatment. Secretion of inflammatory markers increase upon induction of NASH with FFA, LPS, and sugars. Treatment with Elafibranor decreased secretion of these biomarkers. *P≤0.05; **p≤0.005 comparison between FFA+LPS and FFA+LPS/ Elafibranor-treated samples. 

Histological characterization after NASH disease induction with inhibition. Induction of the liver fibrosis associated with NASH is confirmed by elevated expression of stellate cell activation marker α-SMA, ECM markers Col I, Col III, and Col IV. Presence of fibrillar collagens, associated with scarring of the liver, are shown with Sirius Red staining and polarized light. Simultaneous treatment with FFA, LPS, sugars,and ALK5 inhibitor rescues the liver phenotype and halts progression to liver fibrosis.

Model Specifications

  • Human liver model produced with PHH from pooled male/female donors in co-culture with Kupffer cells, hepatic stellate cells, and LECs
  • Guaranteed 28 days viability (before disease induction)
  • 96-well format, 1 microtissue per well

Platform Components*

Catalog #Description
Microtissues
MT-02-302-053D InSight™ Human Liver Microtissues (multi-donor hepatocytes, co-culture with Kupffer cells, hepatic stellate cells, and liver endothelial cells), 96x
Kits
AK-01-001-023D InSight™ FFA-BSA Kit
Media
CS-07-001-01Maintenance Medium – TOX*
(for tox testing), 500 mL
CS-07-212-01Advanced  Glucotox Medium– *
(for NASH induction), 500 mL

* 3D InSight™ Liver Disease Discovery Platform Bundles are customized based on specific partner requirements. Not available separately.

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Human Liver in vitro NASH Model

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3D InSight Human Liver Fibrosis Model Brochure

Brochure: Human Liver Fibrosis Model

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Brochure: FFA-BSA Kit for Steatosis Induction

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