December 6, 2018

expert reaction to study looking at long-term function of genetically modified pig hearts transplanted into baboons

Research published in Nature demonstrates that baboons implanted with genetically modified pig hearts have been able to survive for up to 195 days.

Prof Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said:

“The potential to solve the shortage of available human hearts for transplantation by using pig hearts has been an aspiration for scientists for more than 40 years, but has proved to be a difficult journey.  The biggest hurdle is rapid rejection of the pig heart by the human immune system.  This has been largely overcome by the development of genetically modified pigs, that have successively reduced this complication.  However, it is still not clear whether longer-term organ damage and rejection may remain a problem.

“This new research takes us a step closer to the use of pig hearts in humans.  However the results still fall short of the need for more extensive and longer-term studies before the first pig heart is transplanted into a human.  To be seriously considered for use in humans, studies will have to demonstrate greater success than a mechanical pumping device, and ensure that potential safety complications due to viral transmission from the transplanted heart to the recipient can be discounted.”

Prof Barry Fuller, Professor in Surgical Science & Low Temperature Medicine, UCL & Royal Free London NHS Foundation Trust Transplantation Services, said:

“This is an impressive study on transplantation of organs between species, a process called xenotransplantation.  The possibility to use animal organs for transplantation to overcome organ shortages has been discussed for decades, but has never become a reality because the human body aggressively rejects animal organ transplants because of multiple and strong immune reactions.  Scientists have developed genetically modified pigs which could in theory reduce this strong immune response, but even then, significant problems have remained.

“Langin and colleagues have now shown that by using a new drug regime, alongside a better way of preserving the donor pig heart outside the body, using oxygenated low temperature (+8^oC) continuous perfusion with a new solution including red blood cells, pig hearts survived for more than 6 months after transplantation into non-human primates (another version of xenotransplantation).  The work is also important because it highlights the role that organ preservation may play in stimulating the immune system of the transplant recipient – if the organ preservation is optimised, it can help to damp down the strong immune response to the new organ.

“This new research can thus help both to bring organ xenotransplantation a step closer to human application, and to improve organ preservation techniques for human heart transplantation.”

Prof Christopher McGregor, Professor of Cardiac Surgery, Institute of Cardiovascular Science, UCL, said:

“The publication ‘Consistent success in life-supporting porcine cardiac xenotransplantation’ by Professor Bruno Reichart’s group in Munich is a significant landmark in progress towards transplantation into humans of pig hearts, for the treatment of end stage heart disease.  In the USA and Europe, the need for heart donors is great and exceeds the supply from human sources by at least ten fold.  The Munich groups’ paper brings this transformational treatment closer to active consideration from what was previously only a reasonable possibility.

“Their achievements are longer (up to 195 days) and more consistent (4 out of 5) survival of non-human primates than the less predictable and previous best of 57 days by our group.  These recipients were totally dependent on the transplanted pig heart.  These advances come from improved donor pig heart preservation and better immunosuppressive medicines to prevent rejection after such a xenotransplant.

“It is important to recognise the essential commitment of the large number of experienced investigators and the critical, repeated, high level of German Government research funding underlying this scientific report.  Similarly, application in patients, when it occurs, will have necessitated limited, but essential testing in animals.

“Government, Research Bodies, Health Services and learned Societies would well be advised to now refresh the regulatory environment (particularly the criteria for translation into patients) and review funding needs for the likely possibility of successful clinical xenotransplantation.  The public must continue to be appraised and consulted on this progress of a disruptive 21st century technology with enormous potential benefits to the care of the sick.”

‘Consistent success in life-supporting porcine cardiac xenotransplantation’ by Matthias Längin et al. was published in Nature at 18:00 UK time on Wednesday 5 December 2018.

Declared interests

Prof Barry Fuller: “I have no conflicts of interest.”

Prof Christopher McGregor: “Professor McGregor is Founder of a startup xenotransplantation company FiOS Therapeutics LLC.  Also Professor in the Division of Cardiothoracic Surgery, Director of Cardiac Xenotransplantation, University of Alabama Birmingham.”