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Paolo Rossi Castelli14 Sep 20233 min read

Xenotransplantation: first a heart and now a kidney

Experiment conducted in New York, on a man who had been declared clinically dead. Transplantation of a genetically engineered pig kidney. No rejection in the first 32 days (a record for this type of transplant to date).

Despite disappointments and negative outcomes, cutting-edge research into the possibility of transplanting animal organs—(those of pigs, above all) genetically engineered to reduce the risk of rejection to a minimum—into humans continues uninterrupted. We discussed in our blog, at the time, about the apparent success of the transplant of a pig-heart into a 57-year-old man, who lived on without any particular issues for 47 days before his condition suddenly worsened and he died. We recounted that development in another article.

Now, attention has shifted (or rather, it has returned, after several unsuccessful trials) to kidney transplantation. There is an exceedingly high demand for these organs in the hospitals of the most developed nations, but there are also extremely long waiting lists, so long that sometimes the patients end up dying before their names come up. If animal organs were available for these procedures, this could, ethical issues aside, help to improve the situation.

Observation ongoing

The researchers at the New York University Langone Health Center, who have been working in this field for some time, have been putting large amounts of effort into this type of xenotransplantation (the name for the process of transplanting organs between species).
A team of nephrologists and surgeons asked the family of a 57-year-old man who had been declared clinically dead (and a special hospital ethics committee) for permission to remove both of his kidneys and replace only one of them with a pig kidney. In this way, they could test the pig kidney’s actual ability to function in place of the human ones. The family accepted, and the New York State Department of Health also gave them a green light.

We should make clear that the man was being kept alive exclusively by means of forced respiration and using extracorporeal circulation equipment. Moreover, he had elected to donate his body to science.
The procedure was performed in mid-July 2023 and the pig kidney was continuing to function well, without having provoked any type of rejection, at the 32-day mark, “the longest period to date,” the researchers explain, “that a gene-edited pig kidney has functioned in a human.” Observation is ongoing and the study will continue until mid-September.

Only one gene modified

Unlike in past (unsuccessful) trials using kidneys harvested from pigs that had undergone dozens of genetic modifications, this time the New York-based researchers opted to use a pig kidney with only one modified gene. Specifically, the pig from which the kidney was harvested did not have a protein called alpha-gal, known to cause hyperacute rejection reactions. And this, from what they could tell, made an enormous difference. The pig kidney immediately began to produce urine and demonstrate normal function, without provoking any particular reactions.
To avoid other types of problems that had also occurred in previous xenotransplantation attempts, the kidney to be transplanted was meticulously examined to rule out the presence of a host of different viruses, including porcine cytomegalovirus and porcine endogenous retrovirus (PERV), which have been to blame, due to serious infections or reactions triggered after several days, for the failure of similar past attempts.

“I strongly believe that xenotransplantation is a viable way to help people who are waiting for organs,” said Robert Montgomery, head of the team that carried out the xenotransplant at Langone Health Center. The road ahead, however, looks set to be a long one.

 


 

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Paolo Rossi Castelli

Journalist since 1983, Paolo has been dealing with scientific divulgation for years, especially in the fields of medicine and biology. He is the creator of Sportello Cancro, the site created by corriere.it on oncology in collaboration with the Umberto Veronesi Foundation. He collaborated with the pages of the Science of Corriere della Sera for several years. He is the founder and director of PRC-Comunicare la scienza.

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