The man who received the first-in-human pig heart transplant died two months later, and a pig virus may have been a contributing factor.
Earlier this year, David Bennett – a man with end-stage heart failure – was the first person to receive a heart transplant from a genome-edited pig (see BioNews 1128). The procedure was initially successful, but led to heart swelling and failure two months later. Surgeon Dr Bartley Griffith, who performed the transplant at the University of Maryland, revealed the presence of porcine cytomegalovirus in the patient's bloodstream during a recent webinar by the American Society of Transplantation.
'What was the virus doing, if anything, that might have caused the swelling in his heart? Honestly, we don't know', Dr Griffith said. Immune response to the virus may have triggered a 'cytokine explosion', which is a kind of inflammatory response.
Viruses can remain latent within donor tissues, raising concern about this procedure and the safety of organs from genome-edited animals. Transplant recipients need to take immunosuppressive drugs, to prevent their bodies from attacking the new organ, but also makes them vulnerable to infectious diseases. Porcine cytomegalovirus is not believed to be able to infect human cells, but in the absence of a strong immune response may have been able to flourish within the cells of the transplanted heart.
It is important for the doctors to understand why Bennett died because the next steps in developing the technology would be different if the virus was the problem, or if it was immune rejection.
'If this was an infection, we can likely prevent it in the future', said Dr Griffith. The pig's genome had been edited to avoid triggering rejection, so the team want to know if that aspect, at least, was successful.
Previous research by virologist Dr Joachim Denner from the Free University of Berlin, Germany, showed that the presence of porcine cytomegalovirus was significantly correlated with decreased survival of inter-species heart transplants.
'This patient was very, very, very ill' said Dr Denner. 'Maybe the virus contributed, but it was not the sole reason.'
Approximately 7000 people are waiting for a transplant in the UK, and nearly 7 percent of them died last year waiting for an organ, so new sources of organs for transplant are urgently needed.
State-of-the-art tests are being developed to ensure future transplant organs are free from viruses. Other research groups are using computer models and engineered human and plant tissues, trying to develop organs that can be grown without animals.
Sources and References
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Man who received landmark pig heart transplant may have died of pig virus
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Animal virus found in pig heart used in human transplant
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The dangers of animal-to-human transplants
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Signs of an animal virus discovered in man who received a pig's heart
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The gene-edited pig heart given to a dying patient was infected with a pig virus
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