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NANOSTACKS: A new liver-on-a-chip technology for drug safety testing

Dr Abdullah Talari

Revivocell Limited

Animals to be replaced: Mice, rats, guinea pigs and rabbits

Dr Abdullah Talari is a Research Scientist at Revivocell Limited, focusing on the development of NANOSTACKS™ Organ-on-a-Chip (OOAC) technology. 

At Revivocell Limited, Dr Talari is currently building a 3D-engineered model that accurately mimics the range of different cell types found in the human liver for use in drug safety testing. By using human cells, this model is sensitive and specific enough to predict the development of drug induced liver injury (DILI), which is often not predicted when using animals for drug testing. The model is validated in accordance with the Innovation and Quality Consortium (IQ) and could replace the use of animals in drug development.

The Problem – Drug Induced Liver Injury

Drug discovery and development is a long and expensive process, on average taking over a decade and costing around $2 billon.

The liver is an important organ involved in many bodily functions including food digestion and the breakdown (metabolism) of drugs into inactive forms. Once the liver has processed a drug, it is usually removed from the body through the digestive system. However, drugs can sometimes remain active or be changed into a more harmful form, making them harder for the liver to get rid of. If the drug is taken repeatedly, harmful toxins can build up in the liver and cause damage known as drug induced liver injury (DILI). Most people can fully recover from DILI once they stop taking the drug which caused it, however some people can become very unwell and develop other problems because of it, including jaundice, chronic liver disease and even liver failure.

During drug development, it is difficult to know which drugs are at risk of causing DILI. Drugs are tested in animals before they are approved for human use, but animal livers have many key differences to those of people, including the important enzymes that process drugs. Therefore, some drugs which do not cause problems in animals can cause serious toxicity in humans. On the other hand, some drugs that are discarded after failing animal tests may have been safe and useful for humans, meaning this potentially beneficial medicine is lost. Drug discovery and development is a long and expensive process, on average taking over a decade and costing around $2 billon. Most drug candidates have a success rate of just 10%, with 20-40% failing because of DILI, in part due to animal tests which do not accurately reflect how the drug will work in people.

Due to these issues, the FDA’s Modernization Act 2.0 (2022) now allows alternative methods of drug discovery that do not include animal testing, including organ-on-chip technologies (miniature replicas of human organs on microchips). However, current animal-free liver models cannot represent the full complexity of the cell types found within the liver. Recent advancements in organ-on-a-chip technologies hold promise, however they are expensive and time consuming to use.

Biological building blocksNANOSTACKS

To help with this problem, the team at Revivocell, a spin-out company from Lancaster University, have created an innovative new technology known as NANOSTACKS™, which are “LEGO-like” blocks containing cells. Researchers can stack blocks containing different types of cells to quickly create models recreating the complex mix of cells found in an organ, such as the liver.

The current version of NANOSTACKS™ has been made using some animal-derived products such foetal bovine serum (FBS) which is blood taken from the hearts of unborn cows, and collagen, which is made from pig or cow skin. This project aims to complete testing of NANOSTACKS™ using only animal-free materials, making this technology completely human-specific.

Fail early to improve outcomes for patients

This exciting and unique technology could significantly reduce costs and increase the efficiency of drug development. It is estimated that using NANOSTACKS™ instead of animals in drug trials to predict drug induced liver injury (DILI) development alone could save around $200 million per drug and reduce development time by at least 2-3 years. This technology would allow the selection of drugs with the least potential to cause DILI to move into the next stage of testing. This “fail early, fail fast” strategy could result in improved drug safety for patients and reduced chances of DILI development, lower overall costs and shorter times for drugs to be available on the market. This product could also replace animals in drug development, saving the lives of millions of animals each year, resulting in a win-win for both patients and animals.

Dr Talari plans to share the results of this project at conferences and publish papers in journals so that the data can be used by other scientists and raise awareness to expand the uptake of the technology. He will also use the data to apply for other funding and to attract private investment to further develop the technology, with a particular focus on making it completely animal-free.