Ambitious new UK project to transform human disease modelling

The proposal 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.

The £15.9 million project has been funded by the Medical Research Council (MRC), Wellcome and Innovate UK.

In vitro models

In vitro models use isolated cells and tissues outside the living body.

These can come in many forms, including stem-cell derived cell and tissue aggregates that display some organ features on a smaller scale, called organoids.

They can also include tissue slices removed during surgery, called ex vivo or 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.

This supports the government’s strategy ‘Replacing animals in science: a strategy to support the development, validation and uptake of alternative methods’.

The projects

A coordinated network of five interdisciplinary teams will focus on the development of in vitro disease models of:

• liver
• brain
• cancer
• pain
• blood vessels

MIMIC: An interconnected multiorgan platform to recreate the complex pathophysiology of the metabolic dysfunction-associated steatotic liver disease (MASLD)

One pioneering new project is led by Professor Amir Ghaemmaghami, based at the University of Nottingham.

It aims to develop an innovative multi-organ platform that replicates the disordered physiology of 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.

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 Ghaemmaghami 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.

Edinburgh Human Brain Cluster: Enhancing Investigation of Live Human Brain Slice Models with Deep Patient Phenotyping

One in six people in the UK are living with a neurological condition, including Alzheimer’s and brain tumours.

Now, the team led by Professor Paul Brennan at The University of Edinburgh will be able to study human brains, in the form of small fragments, that have had to be removed from patients during operations.

These samples will provide unique discoveries into real human brain function and the effects of disease.

INTREPID: IN vitro TumouR Explant models for evaluating cancer complexity and Patient Diversity

This team led by Professor Catrin Pritchard at the University of Leicester aims to tackle the barriers associated with widespread adoption of live human tumour tissue explant models, removed during surgery.

These will be used to drive a step change in their use in the cancer research community.

Advanced human in vitro models of pain

Chronic pain affects millions worldwide and remains one of the leading causes of disability.

Effective treatments are limited because current models fail to fully capture pain biology.

This cluster, led by Professor Zameel Cader at the University of Oxford, will develop innovative human models that better replicate the complexity of the pain system.

They will be used to induce pain-like states in the models, with a focus on neuropathic and osteoarthritis pain.

ARTEMIS: ARTificial blood vessels for Thrombosis, Endothelial Modelling, and artificial Intelligence Simulation

Cardiovascular disease is responsible for a third of global mortality, with 85% of those deaths associated with blood clots in the heart, known as heart attack, or brain, known as stroke.

The team, led by Dr Simon Calaminus at the University of Hull, will create adaptable, scalable and reproducible artificial blood vessels which can accurately model key aspects of the human circulation system.

This will help them to ultimately identify safer, more effective drug candidates that can be tailored to different patient needs.

Understanding disease

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.

Improving treatments

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.

Global opportunities

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.

Collaboration

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.