News

Researchers from Nottingham including those at our BRC will lead a pioneering project to look at treating fatty liver disease by developing an innovative multi-organ platform that replicates the make-up of the disease.

The University of Nottingham will receive funding from a £15.9 million investment by the UKRI Medical Research Council (MRC), Wellcome and UKRI Innovate UK will enable the development of advanced, specific and highly reproducible human in vitro models with the aim of making them widely available to researchers in academia and industry.

In vitro models use isolated cells and tissues outside the living body and can come in many forms, including stem-cell derived cell and tissue aggregates that display some organ features on a smaller scale (organoids), tissue slices removed during surgery (ex vivo/explant tissue cultures), and organ-on-chips, which combine cell culture with microfluidics to mimic the structure and function of different organ tissues.

In vitro models will also provide new alternatives, helping to reduce the reliance on animal models in research and drug development, and support the Government’s ‘Replacing animals in science - a strategy to support the development, validation and uptake of alternative methods’, announced recently.

The pioneering new project led by Professor Amir Ghaemmaghami, Professor of Immunology & Immuno-bioengineering, aims to develop an innovative multi-organ platform that replicates the disordered physiology of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), also known as non-alcoholic fatty liver disease.

This is a growing global health concern affecting one in five people in the UK that is caused by accumulation of too much fat in the liver.

The project also includes experts from the University of Edinburgh, University of Southampton, Harvard University, the Quadram Institute and Medicines Discovery Catapult.

MASLD is a multifaceted disease influenced by genetics, metabolism, inflammation, and organ-to-organ communication. Current models, including animal studies, fail to accurately capture the disease’s complexity, limiting progress in treatment development.

Professor Ghaemmagham said: “The project will harness cutting-edge stem cell and organ-on-chip technologies to build interconnected models of the gut, liver, and adipose tissue, key players in MASLD progression.

"Using blood cells from well-characterised male and female MASLD patients with diverse ethnicities, known to have different risks in developing the disease, researchers will generate stem cells to create personalised, patient-specific tissue models, offering unprecedented insight into how MASLD develops and progresses, including the critical transition to liver fibrosis.”

Multifactorial long-term conditions

Professor Guru Aithal, Gastrointestinal & Liver Disorder Theme Lead of the Nottingham BRC, said: “Globally, MASLD is the most common example of multifactorial long-term conditions. There are no animal or laboratory models that can provide us a clear insight into the interaction between different organs that leads to the development of this multifactorial condition.

“Using samples from people who have developed MASLD, we will be able to capture the polygenic architecture of an individual and recreate how dysfunctional link between different organs result in progressive scarring in the liver. Only by systematic investigation of these inter-organ pathways, we will be able to develop and test different treatments that may prevent and treat this condition.”

Professor Patrick Chinnery, MRC Executive Chair, said: “We’re delighted to announce £15.9 million investment to advance human modelling research. This funding supports the government’s ‘Replacing animals in science - a strategy to support the development, validation and uptake of alternative methods’, unveiled today, and is a major step forward in our commitment to developing innovative, non-animal methods.

“Human in vitro models enable the investigation of disease mechanisms whilst minimising the use of animals. This will accelerate our ability to diagnose illnesses early, develop new treatments, and prevent disease."

Dr Michael Dunn, Director of Discovery Research at Wellcome, said: "These novel human in vitro models will help accelerate discovery research by enabling better understanding of fundamental human physiology and disease. We’re pleased to partner with UKRI MRC and Innovate UK to support the development and uptake of these exciting models, which can potentially underpin the development of new and better treatments for a range of diseases.”

Tom Adeyoola, Innovate UK Executive Chair, said: "We're backing scalable human tissue models so companies can get involved early, help shape the technology, and position themselves for global markets. It means better science, less animal testing and real commercial opportunities down the line. That's exactly why Innovate UK is supporting it.”

A key ambition of the new investment is strategic coordination across the network of supported projects and to create connectivity with wider UK capabilities, including industry to join efforts and address common challenges in the field.

The funding was delivered in partnership with the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)