The world's first!
Longinne Health Center, New York University, USA
A few days ago, one was implemented
Special kidney transplant surgery
Doctors have successfully transplanted pigs' kidneys into humans
There is no immediate rejection
Screenshot of the Reuters report
On October 20, Reuters reported that the person who underwent the operation was a brain-dead patient, and his family agreed to participate in the pig kidney transplant test after his body showed signs of kidney failure.
Instead of directly placing the pig's kidneys into the patient's body, the doctors attached it to the patient's thigh blood vessels, which allowed the researchers to observe the patient's condition. After the operation was completed, the transplanted kidney immediately began to work normally, and no rejection occurred in the following 3 days, and some indicators in the patient's body also dropped to normal levels.
The kidney came from a genetically modified pig, and its tissues and organs no longer contain substances known to trigger immediate rejection. Previously, scientists have tried to implant ungenotyped pig kidneys directly into primates, and there is a serious rejection reaction on the spot.
The surgical team checks the pig kidneys (Image: Ap News Agency)
Xenotransplantation brings hope to the contradiction between supply and demand for organ transplantation
For human patients to undergo organ transplants, they must have a suitable organ source. According to the Joint Website for Organ Sharing, there are currently nearly 107,000 people in the United States waiting for organ transplants, of which more than 9,000 are waiting for kidney transplants, while the waiting time for a suitable kidney source averages 3 to 5 years, and 12 people die every day.
Dr. Montgomery, the leader of the study, is himself a recipient of a heart transplant, and he understands the anxiety of waiting for organs. "You have to wait for one person to die and another to have a chance to live, and this traditional approach certainly can't keep up with demand." "I understand this concern in particular, as about 40% of patients currently awaiting a transplant die before they can receive a transplant."
If animal organs suitable for transplantation to humans can be found, the waiting time for patients can be greatly shortened, and the chances of survival will be greatly increased. So for decades, experts have been studying the possibility of transplanting animal organs into humans, but have always had difficulties with the issue of "rejection."
The genetically modified pig kidney used by Dr. Montgomery's team uses gene editing to knock out the alpha-gal of pig genes that are easy to cause rejection. This is a type of galactose that causes the human immune system to attack immediately, knocking it out in the hope of reducing the possibility of rejection.
Pig kidney during surgery (Image source: Associated Press)
Chinese scientists led the birth of the first clinical xenotransplantation prototype
In fact, in addition to the much-watched "pig kidney transplantation" at New York University in the United States, Chinese scientists have also made outstanding contributions in related fields.
There have always been two major challenges in the field of xenotransplantation: (1) pig genomes carry porcine endogenous retroviruses, which may spread to humans and may cause devastating consequences; (2) immune and physiological molecular incompatibilities between pig transplanted organs and humans. That is to say, in order to promote the development of xenotransplantation technology, at least these two major problems must be solved.
On September 22, 2017, the team of Chinese scientist Yang Luhan published a paper in the journal Science, announcing that the first problem has been solved - the cross-species transmission of swine endogenous retroviruses (PERV).
Specifically, the team used CRISPR-Cas9 technology to inactivate all PERV viruses in the primary cell line of pigs, and then bred the world's first batch of PERV active inactivated pigs through somatic cell nucleus transfer, that is, "Pig 1.0".
At a seminar in October 2018, Yang Luhan's team's "Pig 2.0" was announced, and this time the team solved the second problem - the problem of immune rejection of organ transplantation.
Yang Luhan's team used CRISPR to first knock out some of the immune response genes, then insert anti-immune response genes, and edit some of the genes that regulate the coagulation response, thus solving the problem of immune rejection.
At the time, the team expressed hope that the immune response would be further reduced and eventually completely eliminated.
After solving two major problems, "Pig 3.0" was also born.
On September 21, 2020, the results of Yang's team titled Extendive Germline Genome Engineering in Pigs were published in the journal Nat Biomed Eng, a sub-journal of Nature.
This time, the team combined CRISPR-Cas9 and transposon technology to prove that all PERV inactivated piglets can genetically engineer 3 xenoanthins and express 9 human transgenes, thereby enhancing immuncompatibility and coagulation compatibility between pig organs and human receptors.
The team said the 13 genes and 42 alleles they edited were normal in porcine 3.0 physiologically, fertility and germline genetics. Through in vitro tests, cells from "Porcine 3.0" are resistant to human humoral rejection, cell-mediated injury, and pathogenesis associated with coagulation disorders.
Therefore, the team believes that large-scale pig genome engineering studies carried out to improve the compatibility of pigs with the human immune system will eventually make it possible to achieve safe and effective pig xenotransplantation.
The rejection response requires more observation
Of course, the success of a pilot operation does not mean that this operation is no problem, and there are still many problems that need to be solved if it is to be promoted. This time, the pig kidney was only retained for 54 hours, and then it was removed from the person, just a test was done, and there were many safety issues that doctors had to figure out before the promotion.
Zhu Tongyu, vice dean of Shanghai Medical College of Fudan University and a kidney transplant expert, said that he is very optimistic about the development of animal organ transplantation, but there are still many difficulties in practice.
The first is the rejection response of the human immune system. Ultraacute rejection refers to rejection that occurs within minutes to 24 hours after the transplanted organ is connected to the recipient's blood vessels. The biggest achievement of this experiment is the successful overcoming of ultra-acute rejection. Because donor pigs are genetically edited, the galactose gene, a gene in pig organs that causes rejection in the human immune system, is knocked out. Zhu Tongyu called this "a big step in the Long March."
However, ultra-acute rejection was overcome, followed by acute rejection and chronic rejection. Acute rejection is the most common type of transplant rejection, most commonly occurring within 5 to six months after transplantation, while chronic rejection occurs within months to years after surgery. This time, the recipient patient is a brain-dead patient, even if the best life support system is used, it will die quickly, and the follow-up cannot be observed.
Ethical issues need to be explored more
"Pig kidneys are the best source of kidney transplantation in animals, which is the consensus of the academic community." Zhu Tongyu introduced that scientists have done a lot of exploration in animal organ transplantation, and primates have been a popular research direction because of their highest genetic similarity with humans. But primates have many obstacles as donors. For example, the number of baboons is too small to meet the needs of organ transplantation; while monkeys are too light in weight to have organs for human use. Pigs are genetically similar to humans, and their kidneys are similar in size to humans, so they gradually "stand out".
In addition, primates are close relatives of humans and have ethical problems, while pigs are common food for humans, and there is no ethical problem as organ donors. However, there are ethical difficulties in conducting scientific experimental studies using humans as transplant recipients. The ethical aspects of animal organ transplantation in brain-dead patients are still less controversial, but can the trial be expanded to a normal patient population in the future, and can the trial be extended to months or even years? Zhu Tongyu believes: "With our current strict ethical norms, it is very difficult and may require ethical exploration. ”
Then for pig kidney transplantation human body
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