The project, led by the University of Nottingham, is part of a joint investment of £15.9 million by the UKRI Medical Research Council, Wellcome and UKRI Innovate UK in the development of advanced models of human tissues, organs and systems.

These models will be made available to researchers and industry and provide new alternatives for research and drug development and help reduce the reliance on animals in scientific research.

This will support the UK Government’s plans to phase out animal research faster, through the development of a roadmap for alternative methods and models, which was announced by the UK’s Science Minister Lord Vallance today  (11th November).

Innovative models that accurately simulate human disease but in a laboratory are needed to better understand and develop treatments for complex conditions like Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), also known as non-alcoholic fatty liver disease.

MASLD affects one in five people in the UK and is caused by a build-up of fat in the liver. Unchecked, it can lead to inflammation and fibrosis, where scarring leads to damage and ultimately to liver cancer. In the very worst cases this is untreatable and leads to liver failure.

It’s a complicated condition, involving interactions between the liver, gut, immune system and other tissues like the adipose. Whilst researchers can look at these in isolation, there aren’t any models that accurately recreate the condition’s complex nature and the interconnected communication between them. Even studies with animals don’t capture the complexity and the involvement of other factors including diet, genetics and metabolism influence its progression.

To address this researchers from University of Nottingham, including the National Institute for Health and Care Research (NIHR) Nottingham Biomedical Research Centre (BRC), University of Southampton, University of Edinburgh, Harvard Medical School and Brigham and Women’s Hospital and Medicines Discovery Catapult in partnership with STEMCELL technologies have combined their expertise to launch the MIMIC: an interconnected multiorgan platform to recreate the complex pathophysiology of the Metabolic Dysfunction-Associated Steatotic Liver Disease.

The MIMIC project is being led by Professor Ghaemmaghami, who is based at the University of Nottingham. He 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.”

At the Quadram Institute, Dr Naiara Beraza will contribute expertise in the role of the microbiome as a regulatory mechanism of the gut-immune-liver axis during health and disease to the development of this immunocompetent gut-liver-adipose tissue model in healthy and MASLD conditions.

Dr Naiara Beraza from the Quadram Institute said: “We are delighted to be part of this collaborative project with researchers with world-leading expertise and infrastructure in their fields.”

“This project will deliver a technology platform using organ on chip models that will contribute to the replacement of animal use as well as a more rapid translation of research outputs in the clinical practice. The development of this autologous immunocompetent multi-organ system will represent a key step toward personalised medicine”.

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”

The £15.9million funding for ‘human in vitro models’ was funded by Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council (BBSRC) and Engineering and Physical Sciences Research Council (EPSRC), which are part of UK Research and Innovation, jointly with the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) and Wellcome Trust.