Resources

Human liver microphysiological system for predicting the drug-induced liver toxicity of differing drug modalities

Novac et al

The liver is one of the organs most susceptible to drug toxicity and drug-induced liver injury (DILI). With more than 750 FDA-approved drugs known to have a degree of DILI risk, better preclinical models are required to de-risk new therapeutics earlier in the drug development process.​ We assess whether a Liver MPS model could be used to understand the detailed mechanistic aspects of liver toxicity.

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.

Assessing drug-induced liver injury using a sensitive and selective human liver microphysiological system and clinical biomarkers

Novac et al

Drug-induced liver injury (DILI) is the most common cause of acute liver failure and a leading cause of compound attrition in drug development. In this poster, we demonstrate the potential of a liver MPS to better predict toxicity and improve in vitro to in vivo translation.

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Novac et al., 2022

This study demonstrates the capability of a human liver MPS to generate clinically-relevant, high-content data (six endpoint EC50 curves). A broad set of known severely and mildly hepatotoxic compounds to accurately predict human DILI and its mechanism versus conventional approaches.

Multiorgan microphysiological systems as tools to interrogate interorgan crosstalk and complex diseases

Trapecar, 2022

A review of the state of multi-organ microphysiological systems in 2021. Overviews of currently available multi-organ MPS and the different technologies, cells and physiological cues used. Discusses approaches for systems biology integration and how MPS can be more readily adopted in the wider research community.

De-risking drug-induced liver injury through the predictive power of organ-on-a-chip

Unfortunately, it is not uncommon that DILI (Drug-induced liver injury) is only first identified in the clinic. Find out how our systems can help you identify it in your lab.

Fighting Toxic Chemicals: Evaluating the Safety of Cobinamide as a Neutralizing Agent

Webinar Series 4 Episode 3:

This webinar outlines how Boss’ lab used CN Bio’s DILI Services to investigate the hepatotoxicity of two cobinamide formulations.

Predictive DILI Models: Human Liver Microphysiological System for Studying Acute and Chronic Drug-Induced Liver Toxicity

Webinar Series 4 Episode 2:

In this webinar, CN Bio Senior Scientist Dr. Ovidiu Novac discusses how a human liver microphysiological system (MPS), or Liver-on-a-chip, can be used to understand the causality and mechanistic aspects of drug-induced liver injury (DILI).

Characterizing the reproducibility in using a liver microphysiological system for assaying drug toxicity, metabolism and accumulation

Rubiano et al., 2020

This study demonstrated the ability of the CN Bio’s PhysioMimix liver model to generate reproducible results from experiments assaying metabolism, drug toxicity and intracellular accumulation. The results from the paper showed that the liver MPS can be routinely used in general drug evaluation applications.

Interconnected microphysiological systems for quantitative biology and phamarcology studies

Edington et al., 2018

A proof-of-principle study that demonstrates microphysiological systems are capable of modeling multiple organs enabling pharmacological testing of drugs and assessing organ-organ cross-talk, this was done through measuring functional biomarkers for the liver and brain and TEER for the gut and lungs over time.

Perfused human hepatocyte microtissues identify reactive metabolite-forming and mitochondria-perturbing hepatotoxins

Rowe et al., 2018

Undetected hepatoxicity is a major cause of high drug attrition in drug development and drug-related clinical morbidity. This study shows the potential of a liver MPS in mechanistic toxicology and detecting clinical levels of hepatic toxicity earlier in the drug development process.

Integrated assessment of diclofenac biotransformation, pharmacokinetics and omics-based toxicity in a 3D human liver-immunocompetent co-culture system

Sarkar et al., 2017

The paper demonstrates how 3D liver MPS may serve as preclinical investigational platforms for the discovery of a set of clinically-relevant biomarkers, including potential reactive metabolites, endogenous bile acids, excreted proteins, and cytokines to predict early drug-induced liver toxicity in humans.

Integrated gut/liver microphysiological systems elucidates inflammatory inter-tissue crosstalk

Chen et al., 2017

Animal models are the only way to understand the complex systemic effects of drugs in organisms; however, they often fail to translate to humans. Here, we demonstrate the potential of a multi-organ model to study inflammatory organ crosstalk between the gut and liver.