He was one of the great hopes of xenotransplantation for millions of people around the world: almost two months after having made medical history by becoming the first patient transplanted with a genetically modified pig kidney, Richard “Rick” Slayman eventually died at the age of 62. “There is no indication that this is a consequence of his recent transplant”however clarified the Massachusetts General Hospital in a press release. This case marked a major advance in the field of xenotransplantation, which aims to use animal organs to transplant them into humans.
A historic operation
The pig kidney used had been genetically modified to remove potentially harmful porcine genes and add human genes, reducing the risk of rejection of the organ. The feat was made possible thanks to the use of CRISPR-Cas9CRISPR-Cas9“genetic scissors” making it possible to target specific genes to modify in the genome of the donor pig.
“Mr. Slayman will forever be considered a beacon of hope for countless transplant patients around the world and we are deeply grateful for his trust and drive to advance the field of xenotransplantation.”, greeted the hospital. In France, there are more than 18,000 patients with severe kidney failure waiting for a new kidney, and 500 die every year due to lack of an available organ.
Revolutionary: a pig kidney has been successfully transplanted into a human!
Article from Stéphanie le GuillouStéphanie le Guilloupublished on March 28, 2024
THE Massachusetts General Hospital (MGH) recently achieved a remarkable medical breakthrough by performing the first successful transplant of a genetically modified pig kidney into a human patient, marking a new era in the field of transplantation and offering new hope to those suffering from kidney failure. renal.
While the shortage of organs available for transplantation is a major problem, the Massachusetts General Hospital took a monumental step forward by announcing the first successful transplant of a genetically modified pig kidney into a human patient. This surgical procedure, which took place on March 16 and lasted four hours, opens new perspectives for increasing the number of organs available, thus reducing the wait for patients.
A revolutionary medical innovation
Prior to the graftgraftthe porcine kidney has been genetically modified to improve its compatibilitycompatibility with the human organism. The modification geneticgenetic was carried out using CRISPR-Cas9 technology, making it possible to eliminate porcine genes likely to cause rejection and to integrate human genes promoting acceptance of the organ.
The transplant took place in a patient suffering from diabetesdiabetes type 2 andhypertensionhypertension. He had already been transplanted the first time with a human kidney; THE graftgraft lasted five years. The success of this transplant is the culmination of decades of research and innovation in the field of xenotransplantation, or transplantation between speciesspecies different. This advance could significantly reduce waiting times for patients requiring kidney transplants, providing a viable alternative to the shortage of human organs. Currently, in the United States, more than 100,000 people are waiting for an organ, and every day, 17 people lose their lives because a transplant is not available.
Doctors successfully perform experimental pig kidney xenograft on human
Article from Julie KernJulie Kernpublished on August 17, 2023
This is a world first: a genetically modified pig kidney functioned normally and without causing rejection in an experiment on a human. One more step towards xenograftsxenograftsa long-standing dream for doctors who hope to respond to the organ shortage.
Kidneys are among the organs most frequently transplanted by doctors. In 2022, 3,376 people received a kidney transplant in France out of a total of 5,494 transplant recipients, all organs combined. Despite everything, this is not enough to satisfy the demand for kidney transplants and it is estimated that 40% of people on the waiting list are actually transplanted between one to three years after their registration; that’s 15% after five years of waiting.
To deal with this organ shortage, some scientists are working on xenografts, the transplant of an organ of animal origin onto a human. In October 2021, American doctors performed the first xenograft of a pig kidney into a human. Now, doctors at the University of Alabama have repeated the experiment and published the details in Jama Surgery.
A successful xenograft
A 50-year-old man, in a state of brain deathbrain deathwas transplanted with two genetically modified pig kidneys on which 10 genes were knock-off Or knockdown to make them more compatible with the human body and limit the risk of rejection. After the xenograft, the pig kidneys produced several liters of urine and managed to filter the creatinecreatineA wastewaste metabolism produced by the muscles. These two parameters suggest that the two transplanted kidneys perform their functions perfectly.
For the moment, successful kidney xenografts can be counted on the finger of one hand and it is not yet certain that they are safe and effective for the general population and can be carried out as easily as a traditional transplant.
World first of a pig kidney xenograft into a human
Article published October 24, 2021 by Céline DeluzarcheCéline Deluzarche
This is a world first: a genetically modified pig kidney functioned normally and without causing rejection in an experiment on a human. One more step towards xenografts, a long-standing dream for doctors who hope to respond to the organ shortage.
A pig kidney was attached to a recently deceased patient whose family had given their consent. The kidney managed to function for three days, perfectly ensuring its filter and urine production functions, and without causing rejection, announced on October 20 the team of Professor Robert Montgomery who carried out the operation, at the center Langone Health, New York.
The kidney was taken from a pig genetically modified to eliminate a gene producing alphagal, a sugarsugar not present in humans and which usually causes rejection of graftsrejection of grafts animals. Produced by the company United Therapeutics, this pig was approved in December 2020 by the Food and Drug AdministrationFood and Drug Administration (FDA). For three days, the kidney was attached to the blood vessels and kept functioning outside the body. “ The rate of creatininecreatinine of the patient returned to its normal level immediately after the transplant, which shows that the kidney was performing its functions wellassures Professor Robert Montgomery. This gave even better results than with some human kidneys from deceased people “.
Twelve people die every day in the United States waiting for a kidney
“ More than half of dialysis patients see their condition deteriorate significantly or die before they can be transplanted », Testifies Robert Montgomery, himself recently a heart transplant recipient. “ I know what it’s like to be uncertain about when an organ will be available “. In the United States, 90,000 people are waiting for a kidney transplant and every day, twelve die because they did not receive one in time. This experience could lead to real transplants in patients with advanced kidney deficiency. within one or two years “, says Robert Montgomery.
40 years of advances in xenografts
Xenografts (grafts between different species) are an old dream of doctors, who hope to breed animals as “organ reservoirs”. The first real test took place in 1984, where a baby nicknamed “Baby Fae” survived 21 days with a baboon’s heart. Since then, research has developed and doctors have turned more towards pork; the latter being easy to raise, with rapid growth and organs of similar size to those of humans. In addition, its use as a “reservoir” raises fewer ethical questions than with primatesprimates For example.
Heart valves, tendons, pieces of skin or retinasretinas of pigs are already used as temporary or definitive grafts in humans. But today’s operation demonstrates that entire organs can be successfully transplanted, which could pave the way for other types of transplants. In 2018, a baboon survived six months with a pig’s heart.
However, there are still many uncertainties regarding this technique (the details of which have not yet been published). We will first have to ensure that the transplant is viable in the durationduration. Some also fear that xenografts could promote the passage of virusvirus pig in humans. But, for Robert Montgomery, the risk is less than letting patients waiting for a transplant die or seeing their health deteriorate rapidly.
Article from ADIT BE Germany published on 08/16/2005
For many terminal organ diseases, transplantation is the only means of survival. However, there are not enough organ donors worldwide. An alternative is xenotransplantation, which is the use of animal organs and tissues to save human patients.
For all transplants but in particular for this type of transplant, immune reactions are to be feared. “Pig organ transplantation in primates causing a complex cascade of rejection mechanisms”, reports Prof. Dr.Wolf, “We can only overcome this phenomenon in the long term through genetic modification of donor pigs.”
The team of Prof. Dr. Eckhard Wolf and Dr. Regina Klose in Munich have succeeded in breeding a genetically modified TRAIL pig whose organs are a priori protected from human immune defenses. This TRAIL pig presents as a marker on the surface of its cells the proteinprotein human “TNF alpha-related apoptosis-inducing ligandligand“. They are thus protected in vitroin vitro against the cells of immune systemimmune system human. Further studies will need to show whether this mechanism also works in living animals. This will surely require combining different genetic modifications of the donor pigs.
