Genetics

Regenerative medicine: the quest to repair damaged hearts

Close up of stem cells

From heart patches to gene therapy, Anna Clark explains the latest BHF-funded research in the cutting-edge field of regenerative medicine.

What is regenerative medicine?

Regenerative medicine is at the frontier of research. It’s a field of science that looks at different ways to repair (or “regenerate”) damaged areas of the body. This search is particularly urgent when it comes to the heart, which can not easily heal itself if it gets damaged.

One of the most common causes of damage is a heart attack, which occurs when there is a blockage in an artery supplying the heart muscle, so the muscle can not get the oxygen it needs. When this happens, muscle cells can die and over time are replaced by scar tissue. This can mean the heart is not pumping blood as well as it should: a condition called heart failure.

Heart failure can cause constant tiredness, as well as a build-up of fluid in the feet, legs and lungs. Around 920,00 people in the UK are living with heart failure, and although the symptoms can be treated, there is no cure. Heart failure contributes to thousands of deaths in the UK each year.

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Patches to repair the heart

Professor Sanjay Sinha and his team at the University of Cambridge are growing patches of real heart tissue in a dish. The result is a “patch” of heart tissue that contracts in a coordinated way, just like the heart does when it beats. The team aim to graft them onto damaged areas of the heart to repair it.

The process is not simple. They use stem cells – special cells which can become any type of cell in the body. They are mainly found in embryos, but a small number of stem cells remain into adulthood, helping to replenish dying cells or repair damage. They can also be artificially created from adult cells, such as skin cells.

Professor Sinha’s team use both embryonic and artificially created stem cells, giving them a specific mixture of proteins called growth factors to stimulate them into becoming heart muscle cells and epicardial cells (the cells which make the outer layer of the heart). They then put them on a “scaffold” made from collagen (the substance which holds bones, muscles, skin and tendons together) and incubate them for a couple of weeks. During this time, they must be cared for very carefully. The BHF-funded team hope that these patches will revolutionize the way we treat damage to the heart.

Regrowing blood vessels

Scientists we’re funding are investigating ways to encourage the heart to grow new blood vessels, to help improve blood flow into areas that have become damaged.

In 1997, the exciting discovery was made that endothelial progenitor cells (a type of stem cell from the bone marrow) can be found in the blood of adults. These cells can turn into endothelial cells (the cells which line our blood vessels) so are thought to be involved in new blood vessel growth. Scientists are trying to better understand how they could be used to grow new blood vessels in the heart.

Dr Mairi Brittan and her team at the University of Edinburgh have discovered that endothelial progenitor cells might also be found in the adult blood vessel wall. They are now trying to understand more about them, what effects they have and how they could be controlled. In the future, this research could lead to clinical trials to test whether these special cells can repair damaged blood vessels.

Recreating conditions in the womb

In the later stages of pregnancy, more than a third of heart muscle cells in the unborn baby multiply to create new heart muscle. But this regenerative power declines within weeks of birth, and adult heart muscle cells rarely reproduce themselves.

Professor Mauro Giacca and his BHF-funded team at King’s College London are looking at how to stimulate heart muscle cells to multiply, just like they do in the unborn baby. The actions of the cells in your body, including whether they multiply, are controlled by your genes. We still need to learn more about which genes are switched on or off as the heart loses its ability to regenerate, so that we can try to restore this potential.

Professor Giacca and his team are testing nearly 20,000 siRNAs (short sequences of genetic material used to block the effects of specific genes). They will test each one to see how changing heart cells in that specific way affects their ability to multiply.

The team has already identified a sequence of genetic material which could be linked to stimulating regeneration. Professor Giacca hopes that in the future these findings could be used to help switch on the ability of heart muscle cells to multiply and repair the damaged heart, just like they can in the growing embryo. Regrowing hearts might seem like science fiction, but BHF-funded research means this may not be as far off as it first seems.

Published 23 May 2022

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Dr Joanne Taylor

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