A new technique that removes immune cells from donor hearts can reduce the risk of acute rejection following transplant surgery.
Researchers at the University of Manchester, UK, and Lund University, Sweden, have developed the ex-vivo heart perfusion (EVHP) method, which protects and restores the heart when it is removed from the donor, and extends the preservation time for the organs from the current four hours to 24 hours.
This new study, which is published in the latest issue of Frontiers of Immunology, reveals the mechanisms behind acute rejection is down to immune cells in the donor heart migrating into the transplant recipient’s body and being recognised as foreign. The recipient’s immune system is then programmed to destroy the transplanted organ.
EVHP was developed by a team led by Professor Stig Steen from Lund University, while Dr James Fildes from The University of Manchester led the team that analysed donor hearts from pigs before and after EVHP.
They reported that the resident immune cells were significantly depleted and also found the molecular health of the tissue was excellent, resulting in less inflammation.
Using the new technique, the team analysed, preserved and transplanted the hearts in pigs and compared it to the existing method of storing the heart in ice before transplantation.
They found little evidence of rejection after EVHP, even without immunosuppression, while the non EVHP hearts quickly showed signs of severe rejection.
Dr Fildes, who runs the Ex-Vivo Lab at the University of Manchester and the Transplant Research Lab at Manchester Foundation NHS Trust, said: “The technique developed by Prof Steen is a major advance in heart transplantation, as organs can be stored for longer, with incredible preservation.
“What we show in this study is that the technique modifies the heart by removing donor immune cells, which we know drive acute rejection. It also improves the state of the tissue, which reduces inflammation. So this technique has the potential to be a game changer in heart transplant surgery.”
The technique is now being evaluated in humans in a clinical trial across Sweden.
Critchley WR, Stone JP, Liao Q et al. Hypothermic cardioplegic perfusion induces immunodepletion of donor hearts resulting in diminished graft infiltration following transplantation. Frontiers of Immunology 28 July 2020.
https://www.frontiersin.org/articles/10.3389/fimmu.2020.01621/full

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