Improving heart transplant outcomes
Professor Tessa Crompton, Great Ormond Street Hospital Institute of Child Health
Achieved: Autumn 2019
Shine For Shani supports a vital piece for research into child heart transplant outcomes led by Professor Tessa Crompton from Great Ormond Street Hospital Institute of Child Health.
When children have heart transplants, the surgeon must remove their thymus, a gland where white blood cells called T-cells are made, to gain access to the heart.
T-cells help us fight infections, including carefully controlling how and when the immune system responds to invaders like bacteria or viruses.
They are also the cells that can cause a body to reject transplants – because the cells or tissue are seen as ‘foreign’.
Tessa and her team want to improve the short- and long-term success of heart transplants by studying the effects of transplanting thymus tissue from the donor, along with the heart, to see whether this could help stop the recipient’s immune system from attacking the transplanted tissue.
They will also test whether reintroducing part of the patient’s own thymus after surgery will help recover normal immune system behaviour more broadly.
They will initially test this in animals to ensure it will be safe in children.
If successful, this project will enable more successful heart transplants in those children who need them. It could also potentially help children who need other solid organ transplants, such as kidney transplants, and prolong the life of the transplanted organ, allowing children to avoid undergoing major surgery again for longer.
It could also reduce the need for drugs that stop the patient’s immune system from attacking the transplanted organ and improve a child’s overall immune system after transplant.
July 2019 update
We’re pleased to report that the team have met their first key milestone for the project on schedule: setting up laboratory experiments to transplant (mouse) donor thymus tissue into mouse subjects.
These experiments have begun and are progressing well. The idea is to see whether, over time, the new tissue produces working immune system cells that would reduce the risk of the mouse rejecting a heart from the same donor.
This work will provide vital evidence to show whether transplanting thymus tissue from a donor, along with their heart, could stop a child’s immune system from attacking the new organ.
This could have a huge impact on children with serious heart problems who require a transplant, by reducing the risk of rejection and helping the child stay healthier with their new heart for longer.
It could avoid the agonising wait families must go through to wait for a matching donor, as well as the child undergoing another risky transplant.
The team are now expanding their mouse experiments to include transplantation of a combination of donor and recipient thymus. This should show whether children could benefit from being given back some of their own thymus, as well as some of their heart-donor’s thymus tissue. The team are testing this in mice and hope to complete these experiments by October 2019.
After this, they will move onto another series of mouse experiments that involve injecting specially prepared thymus cells to see if this could further reduce the risk of a new heart being rejected.
They will also be studying human thymus tissue – testing whether specific cells can be isolated without affecting how well they work in the body. The project is currently due to complete in summer 2020.
October 2019 update
Professor Crompton and her team have continued progressing their work transplanting thymus tissue from one mouse to another, along with the heart.
The team have also furthered their work on how best to prepare donor thymus for transplant, by examining the impact of freezing the tissue, as this has been shown to reduce the risk of the immune cells in the donor thymus attacking other tissues in the recipient.
Understanding the immune response
The team now want to understand how the immune system behaves after transplant.
To do this they are now investigating the properties of a group of genes, called the major histocompatibility complex (MHC).
The MHC has an important role to play in helping the immune system identify which cells belong in the body, and which are invaders (e.g. viruses or transplanted tissue).
The team will be conducting MHC matching, to determine if a match between the donor and the recipient tissue, could increase the chance of a successful transplant, by helping to stop the immune system recognising the donor tissue as ‘foreign’.
Analysing the benefits of freezing tissue
Professor Crompton and her team have shown that freezing can be used to deplete tissue of thymocytes, cells which develop into T cells.
T cells play an important role in the immune response and reducing the number of thymocytes before transplantation reduces the risk of graft versus host disease, a condition where immune cells in the donor tissue attack the recipient’s own tissues.
The team is working with this industrial collaborator to try out a new freezing technology to determine whether this will freeze solid tissues more successfully than traditional freezing methods.
The team, together with the collaborator, are also in the process of applying for research council funding to follow on and extend the freezing studies using this new technology.