Currently, xenotransplanation is one of the most exciting fields in medical science. The potential of being able to take organs from animals – like pigs – and transplant them into humans is hard to overstate. Organ shortages are a notable problem in modern medicine, with nearly every major organ having long waiting lists for people who need a transplant. Many on the waiting list die before their turn comes.
If those organs could instead be harvested from animals, and safely transplanted into humans, thousands of people could be saved annually. It would revolutionize organ transplantation.
However, the road toward xenotransplantation, and particularly kidney xenotransplantation, has been rocky. Our bodies have a hard time accepting even human organ transplants and trying to transplant animal organs presents yet more problems. Recent attempts to transplant genetically modified pigs’ hearts into people, for example, have only resulted in a few extra weeks of life.
A new study from Nature Communications shows real promise: consistent transplants of swine kidneys into baboons, with positive long-term survival rates, and using only conventional anti-rejection strategies.
Overcoming Organ Rejection: Pig Kidneys in Primates
As the study’s authors outline, previous attempts at transplanting pig organs into primates – human or ape – have been wrought with problems:
- Obtaining and preserving the organs long enough to transplant has been challenging.
- Technical issues or mishaps end some experiments early.
- Even initially successful transplants often fail within a matter of weeks.
- Reporting on actual deaths/outcomes has been spotty, making it hard to determine success rates.
- Anti-rejection protocols have relied on a particular immunosuppression method called the CD40/CD154 costimulatory blockade, which is not approved for human usage.
The latter is a particularly major issue. The CD40/CD154 costimulatory blockade is more effective at preventing xeno-organ rejection than other methods, but it brings a significant risk of causing thromboembolism. That is, large blood clots breaking off from the transplantation site and becoming lodged within a blood vessel, blocking the flow. Because of this, such blockades have not been approved by the FDA for human use.
So, for the study’s authors to say they have successfully transplanted porcine kidneys into a range of baboons, with many seeing better than 6-month survival rates – and without relying on CD40/CD154 blockades – is a big step forward.
The New Kidney Xenotransplantation Process
The experiments were done on previously healthy baboons, removing their existing kidneys and replacing them with kidneys harvested from “10GM” swine with genetic engineering. The genetic modifications were specifically to make the pigs’ organs more acceptable to primate bodies – the same modifications used in pig-to-human transplantation experiments. Even then, organ rejection remains a major concern.
Survival rates for the group varied from 165 days up to 337 days – nearly a full year. The mean and median were 263 and 278 days, respectively. This is a significant improvement over previous experiments.
The study specifically chose baboon subjects which seemed to have the best chances of avoiding instant organ rejection. This has been another challenge in transplantation studies, as some peoples’ and primates’ bodies seem to simply resist transplants without a clear cause. However, utilizing a screening methodology from Johns Hopkins University seemed to produce positive results. This discovery could help improve transplant rejection rates across the board if the methodology holds up in future tests.
Otherwise, the study adhered to accepted standards for the ethical treatment of all animals involved. The donor swine received excellent treatment in life to ensure their kidneys were in the best possible condition.
The authors also note that among the long-term survivors, there was a tendency towards hypercalcemia – too much calcium in the blood. This is an issue of some concern, as hypercalcemia can weaken bones, as well as encourage the development of kidney stones. However, hypercalcemia can be managed through treatment, if necessary.
The Future of Human Xenotransplantation
As a single study, this new process cannot yet be seen as the magic bullet that will make porcine kidney xenotransplantation viable. It will need to be replicated by other groups – but the results presented in the paper are very promising.
In particular, the researchers’ dedication to using FDA-approved processes for organ harvesting, cold transportation, and transplantation, will help improve the odds of their methods improving human experiments. The goal was to be as close as possible to human xenotransplantation, with methods that could translate directly from baboons to humans.
If the results can be replicated on other primates, it will likely only be a short time before the FDA approves human testing of the process. Even if the process were to only work with kidneys, the impact could be impressive. Currently, more than 35 million Americans suffer from chronic kidney diseases, and around 750,000 die each year from kidney failure. Globally, the numbers are even higher, with kidney failure expected to become the fifth most common cause of death worldwide by 2040.
The potential of saving many of those lives is exciting, and we’ll be following this research closely in the future.
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