‘Closer to clinical translation’
“Future studies can refine the approach to lung xenotransplantation and move closer to clinical translation,” they said.
The lung was genetically modified in six genes to remove substances which provoke an immune response in the body, and insert human genes to make the organ more compatible and improve graft survival.
There were signs that the man’s immune system had started ramping up against the organ, which caused some lung damage, but this had started to improve towards the end of the experiment.
The breakthrough was hailed as an important step forward in using animal organs for transplantation.
Beatriz Domínguez-Gil, director of the National Transplant Organisation, said: “This study marks a milestone in translational medicine: for the first time, a genetically modified pig lung has been implanted in a brain-dead human being.
“The significance of this breakthrough lies in the fact that, until now, xenotransplantation experiments in humans had been limited to kidneys, hearts and livers, but never to lungs.
“This organ poses an even greater challenge due to its delicate physiological balance: it receives a very high blood flow and is continuously exposed to the ambient air, making it particularly vulnerable.
‘Critical shortage’
She added: “It opens up an unprecedented avenue towards new alternatives to the critical shortage of lungs for transplantation.”
There are about 150 patients waiting for a lung transplant in Britain each year, but the ongoing shortage of organs means dozens will die waiting for a donor.
About four-fifths of donated organs are not suitable for transplant because they degrade quickly after death and can be damaged because of illness or smoking.
Pigs are considered ideal donors owing to their size, rapid growth and large litters, and because they are already raised as a human food source.
However, transplantation attempts stalled until the advent of the genetic editing tool Crispr, which allows deletions and additions to be made to the genetic code. In recent years, several groups have carried out successful xenotransplantations.
In March, Chinese scientists from the Fourth Military Medical University in Xi’an implanted a genetically modified pig liver into the body of a brain-dead patient for the first time. It survived for 10 days.
Researchers in the US have successfully implanted pig hearts and kidneys into humans.
Professor Iván Fernández Vega, coordinator of the Organoids hub of the ISCIII Biomodels and Biobanks platform, said the recent studies showed that the field was moving forward, but urged caution.
“These studies reinforce that xenotransplantation is entering a clinical experimental phase with reproducible results in several organs.
“This is a single case, which limits the generalisation of the results and requires caution until they are replicated in further studies.
“The transplant was performed on a brain-dead patient, which means that the results cannot be directly extrapolated to living people, as neither the clinical tolerance nor the actual side effects of the procedure can be assessed.
“In addition, follow-up was limited to nine days, so we do not know how the graft would evolve in the medium and long term, and whether additional complications such as chronic rejection or late infections would arise.”
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