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 consists of an advanced microtissue co-culture of healthy primary human liver cells combined with specially formulated media and cocktails that induce the progression of NAFLD and NASH from steatosis to liver inflammation and fibrosis.  Ideal for investigating mechanisms of non-alcoholic steatohepatitis (NASH) induction, in vitro screening of anti-NASH drug efficacy, and safety assessment of drug candidates in a relevant disease background, this powerful model includes all the critical liver cells and inducers needed to recapitulate the progression of human fatty liver disease.

human liver microtissue model before and after lipid loading to simulate NASH phenotype
  • 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, MIP-1α/CCL3, IL-8, IL-6, and IP-10
  • Perform reproducible, throughput-compatible NASH drug screening using a scalable Akura™ plate technology, amenable to a host of certified application endpoints

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 21 days viability (before disease induction)
  • 96-well format, 1 microtissue per well

Platform Components

The 3D InSight™ Human Liver Disease Discovery Platform is a premium 3D cell-based system engineered for NAFLD and NASH  drug discovery and research.  This flexible and scalable solution includes microtissue models, media, inducers, and automation-compatible delivery formats, coupled with services and expert support needed to optimizer your investment in 3D in vitro technology.

Certified Applications

NAFLD and NASH Discovery

Services

NAFLD and NASH Discovery

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Human Liver in vitro NASH Model

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