Resources

Microphysiological system for studying fatty liver disease and its impact on drug-induced liver injury

Kostrzewski et al

As a result of the increased prevalence of diabetes, obesity, and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease in developed countries. Using better in vitro models to fast-track therapeutic development but also accurately assess DILI risk in NASH patients ahead of the clinic is critical. Here, we show the potential of an in vitro 3D NASH model to accurately identify any DILI-associated risks.

Pros and cons of preclinical models of Non-Alcoholic Steatohepatitis

This infographic was made by Biotechniques to help educate people on our NASH-in-a-box kit and how it sets a new standard in the search for an approved NASH therapeutic.

In Focus: Modeling NASH disease – organ-on-a-chip technologies

This short animation describes how our NASH-in-a-box kit enhances your chance of successfully developing NASH therapeutics by recreating our industry-proven NASH model in your laboratory. Created by Biotechniques.

Organ-on-a-Chip Models of Fatty Liver Disease

15-Minute Tech Blast – In this podcast developed by Biotechniques, our Lead Scientist Gareth Guenigault discussed NAFLD & NASH and their growing prevalence both in terms of cases and economic factors.

New Model Will Support Drug Discovery for Liver Disease NASH

Dr Audrey Doubourg discusses the therapeutic challenges of NASH and how our NASH-in-a-box kit will help to advance drug discovery.

This article is taken from Technology Networks, April 2022.

A pressing Need for Accurate Preclinical Models of Metabolic Disease

How using organ-on-a-chip (OOC) can more accurately recapitulate the physiology and functions of the human body by culturing under flow perfusion – to mimic the blood – in 3D.

This article is taken from European Biopharmaceutical Review January 2022, pages 28-31.

β2-spectrin (SPTBN1) as a therapeutic target for diet-induced liver disease and preventing cancer development

Rao et al., 2021

This study shows the effect of the presence of β2-spectrin (SPTBN1) in the promotion of sterol regulatory element (SRE)–binding protein (SREBP)–stimulated lipogenesis. These findings suggest SPTBN1 could be a potential target for a therapeutic against NASH and liver cancer.

Hype or hope – microphysiological systems?

This article in DDW examines MPS (microphysiological systems/organ-on-a-chip) in drug discovery and their place in the preclinical ‘toolbox’.

This article is taken from Drug Discovery World, October 2021.

Modelling human liver fibrosis in the context of non-alcoholic steatohepatitis using a microphysiological system

Kostrzewski et al., 2021

It was shown in this study that the MPS NASH model, composed of a primary cell co-culture in various conditions, is able to model different characteristics of clinical NASH, including advanced disease with a quantifiable fibrosis phenotype as well as pharmaceutical intervention.

Of Mice and Men – Will human organ-on-a-chip disease models replace animal use?

The aim of organ-on-a-chip (OOC) technology is to more accurately replicate human physiology in vitro to overcome the relevance limitations of current approaches, and the field is progressing at a rapid pace!

Pathologically Scarred by Fibrosis: How To Model and Quantify Human NASH in a Microphysiological System

Webinar Series 3 Episode 2:

In this webinar, Dr Samantha Peele, AstraZeneca, and Dr Gareth Guenigault, CN Bio, discuss how to better recreate NASH in vitro, using liver MPS models, to improve the quantification of liver fibrosis.

NAFLD vs MAFLD: could a name change impact the progression of liver disease research?

Read this article to understand why a name change has been discussed in an attempt to reflect its underlying pathology.

How a novel in vitro Liver-on-a-Chip model of fatty liver disease is being used to help prevent a global healthcare crisis.

Find out how our Liver-on-a-chip is being used to help find a therapeutic treatment for NASH.

The Scars of Fat: The Transability of 3D NASH Microtissues To Model Human/murine NASH

Webinar Series 1 Episode 2

Join Dr Michele Vacca, University of Cambridge, to discuss the use of in vitro 3D human and murine NASH models to better understand NASH disease mechanisms.

Bone morphogenetic protein 8B promotes the progression of Non-Alcoholic Steatohepatitis

Vacca et al., 2020

Collaborative publication with the University of Cambridge using the NASH model to bridge knowledge gaps and confirm prior discoveries. This study teases apart the complex, overlapping and multi-faceted inflammatory pathways involved in liver fibrosis to identify key, potentially “druggable”, players in NASH.

A Microphysiological System for Studying Non-alcoholic Steatohepatitis

Kostrzewski et al., 2019

A study that used MPS to resemble key features of human liver tissues with NASH/NAFLD. This study highlighted success in creating an in vitro 3D model for NASH disease modeling, thus facilitating the understanding of the complex mechanism underlying this disease.

Comparing an in vitro Organ-on-Chip model of Non-Alcoholic Steatohepatitis to murine models and liver tissue from patients

Kostrzewski et al

Currently available preclinical in vitro and in vivo NAFLD/NASH models have a range of limitations and do not fully represent the key aspects of the human disease state. This study demonstrates the potential of an in vitro liver MPS model, which recreates and maintains the key markers of the disease, for the assessment of new anti-NASH therapies.

The PNPLA3 I148 variant enhances the disease phenotype of hepatic stellate cells in an in vitro model of non-alcoholic fatty liver disease

Kostrzewski et al

This study demonstrates the potential for a 3D in vitro NAFLD model to (i) explore the molecular mechanisms that underlie the development of human NAFLD, notably the role of PNPLA3 I148 in the severity of the disease; (ii) to analyze the efficacy of novel anti-NAFLD therapeutics against a range of different target pathways.

Fully human in vitro gut-liver model of non-alcoholic steatohepatitis

Kostrzewski et al

Non-Alcoholic Fatty Liver Disease (NAFLD) represents a wide spectrum of liver abnormalities with the most severe cases involving progressive liver injury in the form of Non-Alcoholic Steatohepatitis (NASH). NASH is the liver manifestation of the metabolic syndrome, with close association with insulin resistance, obesity and Type 2 diabetes. The interaction between the liver and the gut (the “gut-liver axis”), is now known to play a critical role in NAFLD onset and progression. Using in vitro human NASH liver and NASH gut/liver MPS models this study shows the potential of such models for the exploration of complex molecular mechanisms and organ-to-organ crosstalk in disease state.

Three-dimensional human cell culture model for studying Non-Alcoholic Fatty Liver Disease

Kostrzewski et al

Non-Alcoholic Fatty Liver Disease (NAFLD) is a growing concern worldwide and is set to become the most predominant cause of chronic liver disease. There are currently no FDA-approved drugs for the treatment of NAFLD and there is a clear requirement for better models to understand disease progression and the molecular pathways underlying the disease. Here, we demonstrate the potential of a 3D human Liver MPS to mimic in vitro the liver microarchitecture and support hepatic functions over extended periods of culture, allowing the continual accumulation of fat deposits in the hepatocytes.