Doctors Thrilled as Pig Kidney Functions in Human Patient for Two Full Months
Victor Tangermann
Sun, September 17, 2023
A pig kidney has continued to function inside of a human body for roughly two months, the longest documented instance of such a procedure, known as a xenotransplant.
It's a promising sign that we could one day start relying on non-human donors for organ transplants, a possible answer to an ongoing organ shortage that has plagued the country for many years. Only around 20,000 people end up getting a new kidney a year in the US, despite there being around 100,000 people on the organ waitlist.
Researchers at NYU Langone performed the transplant on July 14. The recipient was a 58-year-old man who was "declared dead by neurologic criteria before the xenotransplant," according to a press release.
On September 13, or 61 days later, the experiment reached its previously agreed-upon end date, and the man was removed from the ventilator.
In other words, the man was not responsive after receiving the organ, but doctors received his family's consent. Now his remains are with his family.
While that may sound grisly, there are plenty of benefits to this kind of approach.
"In order to create a sustainable unlimited supply of organs, we need to know how to manage pig organs transplanted into humans," said team lead Robert Montgomery, professor and director of the NYU Langone Transplant Institute, in the statement. "Testing them in a decedent allows us to optimize the immunosuppression regimen and choice of gene edits without putting a living patient at risk."
Fortunately, the researchers are optimistic about the latest results.
"We have learned a great deal throughout these past two months of close observation and analysis, and there is great reason to be hopeful for the future," he added. "None of this would have been possible without the incredible support we received from the family of our deceased recipient. Thanks to them, we have been able to gain critical insight into xenotransplantation as a hopeful solution to the national organ shortage."
While it's the longest a pig kidney has survived inside the human body, it's far from the first attempt.
In September 2021, the same team conducted the first-ever xenotransplant of a genetically modified pig kidney to a human, an experiment that was followed up with a second attempt just two months later. Last summer alone, the team tried two more times.
The kidney used in the latest procedure came from an FDA-approved "GalSafe pig," which was engineered by Virginia-based gene-editing tech company Revivicor.
The gene responsible for rejecting pig organs was simply "knocked out," per the press release, allowing the recipient's body to accept the kidney. Additionally, the animal's thymus gland, which remained attached to the kidney, ensured the recipient's immune system didn't start attacking the new organ.
The latest procedure was actually a simplified attempt compared to previous experiments and only included a single gene modification instead of up to ten, according to the statement.
But it wasn't entirely smooth sailing. The man still required immunosuppression medication due to a "mild rejection process" that started one month into the experiment.
In short, plenty more research still needs to be done before we can determine if such a procedure will ever be safe enough for a conventional human patient.
The researchers are now gearing up for clinical trials, which will first require approval from the FDA.
"Why we’re doing this is because there are a lot of people that unfortunately die before having the opportunity of a second chance at life," NYU transplant immunologist Massimo Mangiola told the Associated Press. "And we need to do something about it."
More on kidney transplants: Scientists Intrigued by Bionic Kidney That Survives Inside Pig
Victor Tangermann
Sun, September 17, 2023
A pig kidney has continued to function inside of a human body for roughly two months, the longest documented instance of such a procedure, known as a xenotransplant.
It's a promising sign that we could one day start relying on non-human donors for organ transplants, a possible answer to an ongoing organ shortage that has plagued the country for many years. Only around 20,000 people end up getting a new kidney a year in the US, despite there being around 100,000 people on the organ waitlist.
Researchers at NYU Langone performed the transplant on July 14. The recipient was a 58-year-old man who was "declared dead by neurologic criteria before the xenotransplant," according to a press release.
On September 13, or 61 days later, the experiment reached its previously agreed-upon end date, and the man was removed from the ventilator.
In other words, the man was not responsive after receiving the organ, but doctors received his family's consent. Now his remains are with his family.
While that may sound grisly, there are plenty of benefits to this kind of approach.
"In order to create a sustainable unlimited supply of organs, we need to know how to manage pig organs transplanted into humans," said team lead Robert Montgomery, professor and director of the NYU Langone Transplant Institute, in the statement. "Testing them in a decedent allows us to optimize the immunosuppression regimen and choice of gene edits without putting a living patient at risk."
Fortunately, the researchers are optimistic about the latest results.
"We have learned a great deal throughout these past two months of close observation and analysis, and there is great reason to be hopeful for the future," he added. "None of this would have been possible without the incredible support we received from the family of our deceased recipient. Thanks to them, we have been able to gain critical insight into xenotransplantation as a hopeful solution to the national organ shortage."
While it's the longest a pig kidney has survived inside the human body, it's far from the first attempt.
In September 2021, the same team conducted the first-ever xenotransplant of a genetically modified pig kidney to a human, an experiment that was followed up with a second attempt just two months later. Last summer alone, the team tried two more times.
The kidney used in the latest procedure came from an FDA-approved "GalSafe pig," which was engineered by Virginia-based gene-editing tech company Revivicor.
The gene responsible for rejecting pig organs was simply "knocked out," per the press release, allowing the recipient's body to accept the kidney. Additionally, the animal's thymus gland, which remained attached to the kidney, ensured the recipient's immune system didn't start attacking the new organ.
The latest procedure was actually a simplified attempt compared to previous experiments and only included a single gene modification instead of up to ten, according to the statement.
But it wasn't entirely smooth sailing. The man still required immunosuppression medication due to a "mild rejection process" that started one month into the experiment.
In short, plenty more research still needs to be done before we can determine if such a procedure will ever be safe enough for a conventional human patient.
The researchers are now gearing up for clinical trials, which will first require approval from the FDA.
"Why we’re doing this is because there are a lot of people that unfortunately die before having the opportunity of a second chance at life," NYU transplant immunologist Massimo Mangiola told the Associated Press. "And we need to do something about it."
More on kidney transplants: Scientists Intrigued by Bionic Kidney That Survives Inside Pig
Deidre McPhillips, CNN
Thu, September 14, 2023
Joe Carrotta for NYU Langone Health
A pig kidney successfully functioned in a human body for about two months, marking the longest documented case of a xenotransplant of its kind.
In July, researchers at NYU Langone Health transplanted a genetically modified pig kidney into the body of a 58-year-old man named Maurice Miller, known as Mo, who had a brain tumor and was experiencing brain death. The organ was removed on Wednesday, a predetermined date, after 61 days of study.
Now, the researchers will analyze their findings from this pre-clinical human research to assess the body’s response to the procedure and help prepare for clinical trials in living humans.
For example, tissue collected during the study showed some “novel cellular changes” that required additional immunosuppression medication to reverse a mild rejection, NYU Langone Health shared in a news release. But overall, the kidney was found to perform “optimally.”
“We have learned a great deal throughout these past two months of close observation and analysis, and there is great reason to be hopeful for the future,” said Dr. Robert Montgomery, director of the NYU Langone Transplant Institute and chair of the surgery department, who led the research.
“None of this would have been possible without the incredible support we received from the family of our deceased recipient. Thanks to them, we have been able to gain critical insight into xenotransplantation as a hopeful solution to the national organ shortage.”
In August, another research team published peer-reviewed research on new advancements in transplanting pig kidneys to humans.
Researchers at the University of Alabama at Birmingham Heersink School of Medicine found that transplanted kidneys not only produced urine; they provided the “life-sustaining kidney function” of filtering waste, according to a research letter published in the medical journal JAMA Surgery.
Both research teams used genetically modified pig kidneys that were transplanted into recipients experiencing brain death in what is considered pre-clinical human research. The NYU Langone team used just one genetic modification to “knockout” the alpha-gal biomolecule, which has been found to lead to rapid rejection of pig organs by humans. The pig’s thymus was also transplanted to help protect the kidneys from being attacked by the human immune system.
Researchers say that more work is needed, including studies in living human recipients, to establish whether pig kidney transplants could be a bridge or destination therapy for people with end-stage kidney disease, but they are hopeful about the progress being made.
“We’re gaining critical evidence about how well pig kidneys work in the human environment,” said Dr. Adam Griesemer, surgical director of the NYU Langone Pediatric Liver Transplant Program and the Living Donor Transplant Program, said at a news conference last month.
“Over the last 20 years, we’ve gained a lot of information about how pig kidneys work to replace the functions in primates. But the critical question – ‘Will those data be translated exactly to the human recipients?’ – was unknown. And for the first time, we’re being able to supply that information. So hopefully this also give some assurance to the FDA regarding the safety of initiating phase one clinical trials.”
The vast majority of people waiting for an organ transplant need a kidney. About 89,000 people are on the waiting list, according to data from the US Department of Health and Human Services’ Organ Procurement and Transplantation Network.
Partially formed human kidneys grown inside pigs for the first time
Sarah Knapton
September 7, 2023
A good host – the human kidneys were grown inside pigs - iStockphoto
Humanised kidneys have been grown in pigs for the first time in a breakthrough which could help solve the transplant crisis.
In groundbreaking experiments, Chinese scientists took pig embryos and knocked out two genes needed for kidney development, before inserting human stem cells which had been coaxed back to an embryonic state.
The chimeric human-pig embryos were implanted into surrogate pigs where they developed kidneys composed of 50-60 per cent human cells.
Although the experiment was stopped at 28 days, before the kidneys were fully developed, scientists said they looked structurally the same as normal kidneys, and had started to form tubes that connect to the bladder.
Scientists are hopeful that growing humanised kidneys in pigs could bring a ready supply of organs which would not be rejected by the body.
“We found that if you create a niche in the pig embryo, then the human cells naturally go into these spaces,” says senior author Zhen Dai, of Guangzhou Institutes of Biomedicine and Health in Guangdong Province.
Latest figures from NHS Blood and Transplant show that at the start of September there were 7,228 people waiting for an organ in Britain, of which 5,564 required a kidney.
Pigs are anatomically very similar to humans and are considered the best-suited animal donor candidate. But previous attempts to integrate human cells in pig embryos have failed because pig cells tend to outcompete human cells.
To get round the problem, the scientists genetically-engineered the human cells to shut down natural cell death, so they would not self-destruct when they encountered the pig tissue.
The researchers transferred 1,820 embryos to 13 surrogate mothers. After either 25 or 28 days, they managed to collect five chimeric embryos for analysis, all of which had developed early kidneys.
Despite development, worries exist
Commenting on the research, Dusko Ilic, Professor of Stem Cell Sciences, at King’s College London, said the work was “pioneering” but warned there were still hurdles to overcome.
For example, in the experiments some of the human cells migrated to the brain and spinal cord of the pigs which could bring ethical problems if it caused the animals to develop anything resembling human-like consciousness.
What the embryonic humanised kidneys look like inside the pigs - Wang Xie
There are also animal rights issues of using pigs as ‘incubators’ to grow human organs.
“As the authors admitted, there are plenty of challenges. Will this approach prove to be the ultimate solution? Only time holds the answer”, said Prof Ilic.
“Nevertheless, this captivating strategy warrants further exploration.”
“Undoubtedly, tackling the complexities of [growing nerves] will pose the greatest technical hurdles, alongside the imperative task of preventing human cells from integrating into the animal’s brain.”
Challenges still stand in the way
Experts also warned that turning off human cell death could lead to cancer.
Dr Alena Pance, Senior Lecturer in Genetics, University of Hertfordshire, said: “The concerning issue is that the human pluripotent stem cells are engineered to overexpress two genes, one is a [cancer-causing gene] that maintains proliferation potential and the other is a survival gene that essentially prevents the cells from dying.
“While expression of these genes helps the human cells to survive in the pig embryo their long-term expression and effects on the cells are not described.
“It could perhaps explain why out of 1,820 embryos implanted only five normal ones were analysed.”
Several other labs are attempting to use pigs for organ transplants, and have tried to solve the rejection problem by deleting a gene which produces a molecule that is foreign to humans, but without long-term success.
Last January, US citizen David Bennett, who had terminal heart disease, was given the first heart transplant from a genetically modified pig. But Mr Bennett died two months after surgery.
The new research was published in the journal Cell Stem Cell.
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