Xenotransplantation: Cross-Species Organ Transplants

Written and verified by the veterinarian and zootechnician Sebastian Ramirez Ocampo

Last update: 08 May, 2023

Xenotransplantation is a surgical procedure in which cells, tissues or complete organs from one phylogenetically different species are implanted into another. For example, from a pig to a human being. There are records to show that they have been practiced for at least 300 years, with mixed results that have generated controversy among the scientific community.

Despite this, experts in the field of medicine see xenotransplantation as a possible solution to the shortage of organs that exists today. Discover in the following content the advantages, disadvantages, and perspectives of this practice in the future of human health.

The shortage of human organs and the need for new solutions

According to data from the Global Observatory on Donation and Transplantation, 150,000 human-to-human transplants are performed each year worldwide. However, in countries such as the United States, donation is still very low, and, on average, 17 people die every day waiting for a transplant of vital organs such as a heart, liver, or kidneys.

Likewise, the European Directory for the Quality of Medicines and Health Services determined that, even though 36,000 patients received a transplant in 2021, 41,000 new patients were added to the waiting lists.

Due to this problem, doctors and researchers have become interested in using organs from animals. In particular, pigs and non-human primates (NHPs).

Animals used in xenotransplantation

The first reported case of xenotransplantation occurred in 1667, when the French physician Jean Baptiste Denis transfused lamb blood to a young man with fever and obtained positive results. However, this practice didn’t have the same success in other patients, so xenotransfusion was banned in France for many years.

Later, in 1920, surgeon Serge Voronoff transplanted chimpanzee testicles into a group of men with the aim of increasing virility, energy and vigor. However, the benefits failed to be scientifically supported.

Years later, between 1963 and 1993, several xenotransplantations of kidney, heart, and liver organs from primates to humans were performed. Although most patients died within hours or days after the procedure, there was one case in which a person survived for 9 months with a chimpanzee kidney without apparent complications.

The downside with non-human primates

Although one might think that NHPs are ideal candidates for xenotransplantation in humans, the reality is that their viability as a source of organs is quite controversial. On the one hand, being endangered animals, their use for this practice is presented as unethical.

In addition to this, there’s a risk for the recipient to develop primate-transmitted diseases. This is due to the amount of genetic information we share.

Likewise, in practice, it has been observed that they don’t provide organs of an adequate size for humans. In addition to being rejected in most cases by the immune system of the human recipient.

The pig: donor of the present era

Faced with such drawbacks, most modern research focused on another species, the domestic pig. These pigs, which have been subjected to numerous experiments in recent years, have ideal characteristics for xenotransplantation:

• They have anatomical and functional similarity to humans
• There’s a large number of specimens all over the planet
• Their reproduction is easy and their gestation is short
• They can be bred free of pathogens

However, despite the great progress made with the species, there are still two major problems with pigs: immune rejection and the risk of infection.

Obstacles to xenotransplantation

Rejection occurs because the human immune system recognizes the transplanted organ as a foreign body. Therefore, an antibody response is generated that binds to the endothelial cells of the graft in an attempt to destroy it. This rejection reaction can occur in a matter of hours, days, or months.

To solve this problem, researchers have sought to genetically modify donor pigs in order to trick the recipient’s immune system. For example, by creating transgenic animals that express human genes with immunomodulatory capabilities that prevent rejection.

As for infection, the risk lies in the transmission of specific pathogens from porcine tissues or in the transmission of retroviruses hosted in the pig genome. The latter can silently infect humans by integrating and altering the composition of genes, causing disease or xenozoonosis.

However, thanks to genetic manipulation techniques such as the CRISPR tool, it has been possible to inactivate these retroviruses in the pig genome.

Recent studies on xenotransplantation

In 2022, the first heart transplant from a genetically modified pig to a human with end-stage heart failure was performed. Initially, there was no rejection by the recipient individual.

However, he died after eight weeks when he developed a porcine herpesvirus infection. This virus, which causes Aujeszky’s disease in pigs, couldn’t be identified in the pre-transplant studies.

On the other hand, a recent article published in The New England Journal of Medicine reported how kidneys from transgenic pigs functioned well in the bodies of two people. However, this was a more experimental and demonstrative study, as the human patients were brain-dead.

Is xenotransplantation a possible solution?

Undoubtedly, the demand for organs by human beings is a latent problem. Moreover, with the exponential population growth in recent years, the need for transplantation is expected to increase.

While xenotransplantation could provide an unlimited supply of organs, there are still many questions that science must resolve before this technique can be implemented routinely.

Therefore, more research is needed to support xenotransplantation as a safe and functional practice over long periods of time.