Developing a blood clot-on-a-chip model to find new ways of treating heart attacks

Professor Nicola Mutch at the University of Aberdeen is developing a human-relevant model to reveal insights into blood clot formation and breakdown and what goes wrong in conditions such as coronary heart disease. This could lead to more effective drugs for a range of conditions and the replacement of animals used in this research.

Blood clots – friend or foe?

Our blood needs to flow continuously and smoothly but also needs to quickly form clots to prevent blood loss when we are injured. Clots are formed when chemical triggers, sparked by blood vessel injury, cause tiny cell fragments in the blood, called platelets, to clump together. Through a series of chemical chain reactions, a clot made from platelets and proteins is formed to block the leak.

Clotting is a tightly controlled process. Chemical signals set a limit and eventually cause the clot to breakdown as damaged blood vessels heal. Sometimes however, this process goes awry and blood clots form when they aren’t needed or they don’t break down, blocking blood vessels instead. If blood vessels that supply the heart (coronary arteries) are blocked by clots, it can lead to a heart attack.

Every five minutes someone is admitted to hospital in the UK as a result of a heart attack. This represents a significant healthcare and financial burden. Current clot busting therapies carry the risk of bleeding and are not recommended for certain people, for example if they have previously had a stroke.

Understanding how and why these blood clots form is vital so that we can develop better therapies that break down the clot whilst minimising the risk of bleeding. 

Animals used in blood clot research

Animals have traditionally been used to study blood clot formation. They are either put under general anaesthesia and clots induced by damaging blood vessels or are injected with chemicals to induce clots, which leads to considerable pain and suffering. They are subsequently killed so their tissues and blood can be studied.

Large numbers of animals (over 2000 mice each year in the UK alone) are used for each experiment so that the results can be considered reliable. However, reliance on animals means that crucial information about how blood clots form in people is being misinterpreted or even missed. Mice for example, have different proteins and chemicals that control the formation and breakdown of clots.

A more human-relevant way of studying this process is urgently needed to save more lives.

 

Developing a new model to study blood clots

Professor Nicola Mutch, at the University of Aberdeen, has developed a human-relevant, animal free model that mimics blood vessels and enables the study of blood clot formation. The model uses a transparent, flexible chip with tiny channels through which micro amounts of human blood can flow. This microfluidic model can simulate the way blood flows within different blood vessels. The rate of blood flow can be altered – this is a factor which has been shown to directly impact the formation and stability of blood clots.

To improve the model so that it better reflects blood vessels, Professor Mutch is now incorporating vascular endothelial cells (VECs) which are found on the inner lining of heart blood vessels. These cells supply a number of factors that influence the clotting process, so their inclusion in the model will help Professor Mutch to assess their influence on clot breakdown. She’s using VECs from healthy individuals and those with coronary heart disease (where blood vessels supplying the heart are narrowed or blocked) to find out what goes awry with the clotting process during coronary heart disease.

Professor Mutch will use sophisticated microscopy to visualise the proteins and chemicals involved in the formation and breakdown of blood clots.

Impact of the research: benefits for humans and animals

This model could enable researchers to better understand mechanisms underpinning human stroke and to develop improved clot busting treatments for coronary heart disease more quickly and cost effectively. This microfluidic model could also be adapted to include cells from different blood vessels, such as veins and arteries, which, due to structural differences from coronary arteries, may respond differently to clot busting therapies. This would give the model great potential for the development and testing of a range of anti-clotting drugs for various conditions.

Professor Mutch and her team plan to promote the model and share their knowledge and designs with colleagues and collaborators in the field who are still using animals in their research. This could have a significant impact in saving people’s lives by uncovering more effective treatments, using better tools and ending animal suffering.