Testing potential older organ donors for dangerous zombie cells could help increase the number of hearts available for transplantation, according to research partially funded by the British Heart Foundation and presented at the British Cardiovascular Society conference in Manchester this week.
Hearts from donors over the age of 65 are not accepted for donation due to the likelihood of an unfavorable clinical outcome. However, our hearts age at different rates, and age isn’t necessarily the best predictor of heart health.
Researchers at the University of Newcastle in the UK are working to develop a test that can help doctors quickly determine whether a donor heart may still be eligible for a transplant. With around 320 people currently waiting for a life-saving heart transplant, it is hoped this new test will help increase the number of hearts available and enable more people to get the transplant they desperately need.
Research has shown that people with heart disease have more senescent (zombie) cells than those without, after finding higher levels of zombie cell markers in their blood.
The zombie cells aren’t dead, but they don’t function as they should. They release molecules that can target nearby cells, turning them into zombie cells as well. They also increase the amount of inflammation and cause scar tissue to build up in the heart muscle. This increases the risk of developing heart and circulatory diseases.
Study the signatures of zombie cells in the blood
The team now wants to learn more about the footprint zombie cells leave in the blood and what that tells them about biological age versus the chronological age of the heart. They think a blood test to look for this signature in older potential donors could reveal those who have biologically young and healthy hearts who may be suitable for transplantation.
Our work is revealing more about the clues zombie cells leave behind to suggest their presence in the body, said Gavin Richardson, PhD, senior lecturer and subject head of vascular medicine and biology at Newcastle. We are hopeful that we will be able to use these clues to better understand which unsuitable donor hearts might be used after all.
This could be a game changer as most older donor hearts are not being used for transplant, but the hope is that we will be able to demonstrate that a number of these organs are suitable for transplant for people waiting. desperately a new heart.
When the team examined human heart cells in a dish, the researchers saw that the zombie cells secreted higher levels of the GDF15 protein than healthy cells. Using blood samples from 774 people over the age of 85, the researchers then found higher levels of the GDF15 protein in the blood of people with heart disease than people without suggesting their hearts contained more zombie cells.
The increase in GDF15 levels in the blood of people with heart disease was similar to that of another protein already used to diagnose heart failure, making researchers hopeful they could identify cells associated with senescence.
The team also looked at the RNA in cells from eight donor hearts. RNA tells cells which proteins to make depending on which genes are turned on. When the researchers looked at another marker in these hearts linked to zombie cells called p21, they found a strong link between it and another marker of heart and circulatory disease.
The researchers believe these two molecules will be part of the zombie cell signature that could be detected through tissue or blood tests. They are now using blood and tissue samples from the Quality in Organ Donation and NHS Blood and Transplant biobank to look for this signature and find out if it is linked to better transplant outcomes.
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