With the demand for transplants exceeding the supply of organ donors, pig may serve as a viable alternative. On March 21, 2024, scientists performed a historic event by xenotransplanting a pig kidney into a living human being for the first time ever.
This achievement has engendered worldwide optimism regarding a novel turning point in the field of medicine. Clacified, in this article, provides information on five additional organs that have been the subject of xenotransplantation trials and evaluations from pigs to humans.
For meat-eaters, pork is synonymous with steaks, fillets, bacon, sausages, ham and even pig's trotters. However, given the stagnant number of human organ donors, a physician well-versed in the most recent developments regarding organ transplantation will find pigs to be an exceptionally intriguing resource other than food.
Professor and physician Pierre Gianello of the Catholic University of Louvain's experimental surgery and transplantation centre holds the view that pigs represent the future of humanity.
Human-to-animal transplants, also known as xenotransplantations, were unsuccessful for decades due to the rejection of foreign tissue by human immune systems.
Today, researchers are endeavouring to successfully replicate the experiment utilising genetically modified pigs that exhibit a greater resemblance to human organs.
Pigs are ideal organ donors due to their size, rapid growth, and large litter sizes. In recent years, for the purpose of determining their efficacy, researchers temporarily transplanted kidneys from genetically modified pigs into brain-dead donors.
The xenografts pose a significant obstacle due to the propensity of the recipient's immune system to mount an attack on the foreign organ. To mitigate this risk, genetic modifications are applied to pig organs.
Additionally, two individuals who received heart transplants from pigs perished within a few months.
The potential authorization of a limited number of Americans in need of a new organ to participate as volunteers in rigorous studies involving pig hearts or kidneys is being investigated by the U.S. Food and Drug Administration.
Although one might assume that primate populations are in the greatest position to provide us with such organs, this is not always the case. Furthermore, documented instances of primate-to-human contamination exist.
Nevertheless, pigs and humans share a number of characteristics, including cardiac and renal functions, as well as the regulation of blood sugar. An additional benefit is that pigs have been mass-produced by humans, albeit with varied outcomes. They produce numerous litters and reproduce rapidly. Thus, investigations were initiated to examine the viability of pig-to-human xenografts.
What risks are involved? The initial and most apparent barrier is rejection.
Not surprisingly, the human body rejects DNA from pig tissue immediately. For the purpose of minimising the risk of rejection and "turning off" specific genes while adding others, cloning research was required.
While there is currently no evidence of pig-to-human xenografts, investigations into pig-to-primate xenografts show considerable promise. Baboons in the United States have been subsisting on pig organs for the past three years.
Before we witness the liver transplantation of a pig into a human, however, pig organs can be utilised as "intermediate grafts," which could aid in the survival of a patient awaiting a human organ donation or accelerate the healing process.
Several nations, including Belgium, Germany, the United States, and Spain, are conducting xenotransplantation trials, which involve the transfer of cells and tissues from one species to another.
Furthermore, it is important to acknowledge the distinctly peculiar nature that underpins the very concept of xenotransplantation. How would you feel if the liver or heart of a functional pig were implanted within you?
Despite the likelihood that an individual in your social circle possesses pig heart valves or knows someone who does, there remains a significant disparity between chemically treated tissue and living, functional organs.
In mid-January 2024, a genetically modified pig's liver effectively filtered human blood from a brain-dead corpse for three days, representing a significant milestone in the development of a liver-specific "dialysis" system that has the potential to preserve lives.
This event transpired in the United States, where surgeons affiliated with the University of Pennsylvania declared success in the transplantation of a brain-dead human being with a liver that had been genetically modified.
Throughout the seventy-two-hour study period, the organ maintained its optimal functionality in an enormous triumph demonstrating that the use of pig organs is a direction that the scientific community has every reason to pursue further.
The liver is distinct from the kidneys and heart in that it produces substances required for other bodily functions, filters blood, and eliminates debris.
The objective, as described in Wired, is to stabilise patients awaiting a human liver transplant with these pig livers rather than performing a definitive transplant.
A few days of operation time could therefore be sufficient to save the life of a patient in the terminal phase of liver disease if a definitive transplant is not possible.
Additionally, pig liver can provide patients whose own livers are functional but require time to recover with transient support.
The study was conducted by Abraham Shaked, a surgeon affiliated with the Transplantation Institute of the University of Pennsylvania. He characterises it as "a method to improve the likelihood of recovery," potentially obviating the need for transplantation.
Dr. Shaked's staff spent three days working on the pig liver transplant due to an early decision by the family of the brain-dead patient to discontinue the experiment.
Throughout this period, the pig's liver executed its function flawlessly by generating bile and preserving an optimal acidity level in the human's blood, which remained constant.
Annually, in the United States, the number of individuals requiring liver treatment exceeds 330,000, with over 10,000 presently awaiting a liver transplant (for an estimated 103,000 Americans awaiting an organ transplant).
In recent years, numerous endeavours to transplant organs from animals to humans have been unsuccessful. Particularly when they originate from an alien species, these foreign tissues are simply rejected by our immune system.
This time, the physicians adopted a different approach. In an innovative experiment, the pig liver was surgically implanted into a human body while it remained externally positioned.
The scientists were thus able to observe in real time, as reported by the AP press agency, the passage of the patient's blood into the pig liver for filtration while in a condition of brain death.
This organ had to be genetically modified to resemble the human liver more closely, and then preserved in a system that normally maintains donated human livers "alive" prior to transplantation.
David Bennett, who died in March 2022, was initially the first human to survive for two months while carrying a genetically modified pig heart in his ribcage. Then, on November 2, 2023, Lawrence Faucette, age 58, passed away following his September 20 transplantation, which exhibited comparable attributes.
Both individuals were diagnosed with a terminal cardiac condition and sought treatment at the University of Maryland Medical Centre in Baltimore.
Bennett and Faucette were both too ill to receive conventional transplants. They had everything to gain and almost nothing to lose. The surgeons who attended to them are optimistic that their expertise can propel medical advancement.
The institution stated that Lawrence made substantial progress in the six weeks subsequent to the operation. He engaged in physical rehabilitation, spent time with his family, and "conducted a card game with his spouse, Ann."
The University of Maryland reported that although the graft initially appeared to be effective, the patient began to exhibit indications of rejection in the days that followed.
The precise nature of the error that transpired in Faucette's case is still unknown. It was concluded that the production of antibodies by Bennet's immune system was the cause.
Traces of porcine cytomegalovirus, a dormant virus unique to pigs, were also detected in the heart, which may have played a role in the complications that arose during the transplant.
United Network for Organ Sharing (UNOS) data indicates that 42,887 organ transplants were performed in the United States in 2021, representing a 3.7% increase from 2021 and a new annual high. 3,817 in total were intended for the heart.
Revivicor, a Blackburn, Virginia-based organisation responsible for the heart, is a leader in the field of xenotransplantation. Established in 2003, the organisation evolved from PPL Therapeutics, a British firm renowned for its role in the 1996 cloning of Dolly the sheep, the inaugural mammal derived from an adult cell.
In March 2024, physicians from Massachusetts General Hospital announced that the world's first transplant of a genetically modified kidney from a pig to a living human had been effectively completed.
62-year-old Rick Slayman, a resident of Weymouth, Massachusetts, and recipient of this epoch-making procedure, was diagnosed with end-stage renal disease.
Slayman disclosed in a written patient statement provided by the hospital that he had been a participant in the transplant programme for a period of eleven years. Slayman has previously undergone a kidney transplant.
In 2018, following years of enduring diabetes and hypertension, he was granted one by a human carer. Five years later, that kidney exhibited indications of failure and he recommenced dialysis in 2023.
His physicians advised him to attempt a pig kidney after they diagnosed him with end-stage kidney disease a year ago, according to him.
Slayman stated in the written statement, "I saw it not only as a way to help myself, but also as a way to provide hope to the thousands of people who need a transplant to survive."
The surgeon who performed the operation, Dr. Tatsuo Kawai, director of the Legorreta Centre for Clinical Transplant Tolerance, stated that the organ was precisely the same size as a human kidney.
Kawai asserted that the kidney prompt "turned pink" and commenced urine production upon insertion. The operating room was filled with jubilant acclaim.
"It was without a doubt the most exquisite kidney I have ever beheld," Kawai declared during a press conference.
At a press conference, physicians reported that Slayman is making a speedy recovery and will be discharged from the hospital in the near future.
The pig organ was genetically modified by the company eGenesis in order to increase its compatibility with humans.
The demand for organs significantly surpasses the actual supply. A mere seventeen individuals perish daily in the United States while awaiting an organ transplant; kidneys are particularly scarce. Approximately 27,000 kidneys were transplanted in 2023, according to the Organ Procurement and Transplantation Network; however, there were still around 89,000 individuals waiting in queue for these vital organs.
It may seem unbelievable, but insulin, the hormone that regulates blood sugar levels and protects against diabetes (type 1 and type 2), is secreted by a 2% portion of the pancreas. Diabetes is a disease on the rise that affects 11% of the population with 10% of diabetics being type 1 diabetics.
For many decades, the medical field has utilised insulin, a substance derived from pig, to alleviate human suffering.
Insulin derived from pigs (and bovines) was used to treat diabetics between the 1940s and 1980s, as synthetic insulin production did not commence until the 1980s.
Despite this new discovery some diabetic patients continued to prefer purchasing insulin from pigs.
Adrián Abalovich, an Argentine physician, surgeon, and emergentologist, performed an innovative experimental procedure over a decade ago by transplanting islets of these cells, termed Beta, into 22 type 1 diabetic patients whose pancreas had ceased producing insulin due to an autoimmune reaction; therefore, they required external insulin delivery.
60% of their blood glucose levels, which in many cases were extremely unstable and caused severe disruptions to their daily lives and futures, were brought back into balance by the procedure.
Abalovich and his colleagues introduced this microencapsulated pig islets into patients' abdomens via laparoscopic surgery (tiny incisions).
They accomplished this by microencapsulating them and ensuring that the recipient organisms would not reject them after isolating them. And subsequent to that, life changed and improved for many of them.
The research conducted by Abalovich et al. established that the transplantation of pig cells does not pose a risk of pig endogenous retrovirus (PERV) transmission; this finding paved the way for the ongoing practice of pig organ transplants to humans.
Abalovich and his team were the physicians who performed the inaugural heart transplantation from a genetically modified pig on January 10 mentioned above. This historic event saved the life of David Bennet who was gravely ill and had no treatment options.
The duration of the protocol approval process exceeded two years. The islets were imported from New Zealand specifically for the initial transplant, which occurred in August 2011
In an August 2022 pilot study, a scientific team devised a pig skin collagen protein implant that emulates the human cornea and successfully restored vision to twenty patients with degenerative corneas (predominantly blind prior to implant insertion)
The goal is to develop a bioengineered implant that can serve as a substitute for the transplantation of human corneas donated by donors, a resource that is in short supply in the nations with the greatest demand.
The research was conducted in collaboration between Linkoping University (LiU) and the Swedish firm LinkoCare Life Sciences AB with Nature Biotechnology publishing the findings.
The aim is to develop a bioengineered implant that can serve as a substitute for the scarce and critical practice of transplanting donated human corneas, which the authors describe as "promising results that provide hope to those suffering from corneal blindness and low vision."
"The results show that it is possible to develop a biomaterial that meets all the criteria to be used as a human implant, that can be mass produced and stored for up to two years, and thus reach more people with vision problems," according to Neil Lagali in a statement issued by the LiU.
One in every 12.7 million individuals globally is blind due to injury or disease of the corneas, the most transparent layer on the eye; therefore, cornea transplantation derived from a living donor is their only effective treatment option.
However, only one in every seventy patients is successful in receiving this transplant. Moreover, a significant proportion of those requiring it reside in low and middle-income nations, where the availability of treatments is extremely restricted.
Professor Mehrdad Rafat of LiU and founder and CEO of the company that manufactures the bioengineered corneas used in the study stated, "We have made substantial efforts to ensure that our invention is widely accessible and affordable for all, not just the wealthy."
The cornea is composed predominantly of the protein collagen. To construct a substitute for the human cornea, the scientists utilised collagen molecules extracted from pig skin that had been subjected to rigorous processing conditions suitable for human consumption.
Pigskin, a byproduct of the food industry that was utilised by the researchers, is readily available and cost-effective.
During the fabrication phase, the group secured the adrift collagen strands, resulting in the formation of a resilient and impermeable substance capable of withstanding implantation within the eye.
Bioengineered corneas can be retained for a period of two years prior to use, whereas donated corneas must be utilised within two weeks. Additionally, the researchers developed a novel minimally invasive surgical technique that eliminates the need for sutures and merely requires a tiny incision to insert the implant into the cornea.
In Iran and India, where a considerable number of individuals endure corneal blindness and low vision, surgeons employed the surgical approach and implants in lieu of viable treatment alternatives and donated corneas.
Twenty individuals who are blind or on the verge of losing their vision due to advanced keratoconus—a disease characterised by a corneal thinning that can result in blindness—were enrolled in the pilot clinical trial and were fitted with the biomaterial implant.
The procedures transpired without incident, the tissue promptly recovered, and an eight-week course of immunosuppressive eye drops was sufficient to avert any potential rejection.
The patients were monitored for a duration of two years without encountering any complications. The implant must be approved by regulatory authorities following a comprehensive clinical study.
Since pig skin is a perforated, two-millimetre-thick fabric that conforms to the contours of any individual, it can be utilised to treat burns, ulcers, and incisions. This tissue has been housed at the Carlos Andrade Marín Hospital (HCAM), which is a Social Security institution, since 2016.
In 2018, a biotechnology company was granted authorization by the Food and Drug Administration (FDA) in the United States to conduct the inaugural pig skin transplant to a human recipient.
Pig skin functions akin to a blanket in that it functions as a transient graft with a purpose to prevent the spread of infection to incisions.
The epidermis of this animal is referred to as "pigermis" or "xe xenograft," which means "extra-species organ or tissue." Its benefits include the provision of additional space for patients with intermediate to severe burns to recover.
This impermanent covering is removed after aiding in the healing or scarring process and does not remain "stuck" on the individual's skin. "Because the length of stay is decreased, the individual evolves at a quicker rate."
Also receiving the xenograft are patients who have ulcers or bleeding lesions.