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Author: Daisy
Introduction: On November 1, researchers published in Science showed that the first case of pig kidney transplantation to brain death published last month did not show rejection, and the genetically engineered pig, a gene encoding alpha-gal (called alpha-gal glycan) (which causes antibody-mediated acute rejection of pig organs in humans), was removed in donor pigs and can be used as a donor of skin and nerve grafts, a provider of long-term heart valves. as well as sources of allergy-free meat. But the study didn't bring any cross-species organ exchange, and now it's just a short-term assessment of xenotransplantation in brain-dead people. Xenotransplantation may cause serious rejection reactions, resulting in the killing of its own immune cells; secondly, there may be viruses, causing immeasurable harm to the recipient, etc. True xenotransplantation also requires a lot of scientific experiments and data.
Others say that while the study leaders claimed that the procedure offered "new hope for an unlimited supply of organs," the much-publicized transplantation of genetically modified pigs' kidneys into brain-dead human recipients last month did not bring about any cross-species organ exchange. Still, genetically engineered pigs may be less flashy in their uses today: as donors of skin and nerve grafts, providers of long-term heart valves, and sources of allergy-free meat.
Xenotransplantation is the surgical transplantation of organs or tissues from an individual of one genus to a certain part of an individual of another genus. Scientists have bred new organs on the animal body, these organs are covered in the human stem cell cultivation environment, the development of new organs can be accepted by the human body, as long as the human body receives these "xenotransplantation" does not cause a tragic immune system response, which will form a de facto steady stream of human transplant organ sources, thus effectively solving the current situation of serious shortage of human transplanted organs. However, at the same time, the organs cultivated by xenotransplantation are transplanted into the human body, and there will be problems such as cross-species virus infection.
On November 1, researchers published an article in Science titled "Skin, nerve transplants from genetically modified pigs could help humans, but organs are a way off."
doi: 10.1126/science.acx9527
Transplant studies conducted at New York University have shown that the human immune system does not immediately reject the organs of a genetically engineered pig that lacks alpha-gal, a sugar molecule that drives the human immune system into a frenzy. Pig kidneys filter waste from the bloodstream and produce urine for at least 54 hours. After that, the doctor turned off the recipient's ventilator and ended the experiment.
But Wayne Hawthorne, a transplant scientist at Australia's Westmead Institute of Medicine and president of the International Xenotransplantation Association, said the findings were "not surprising." The International Society for Xenotransplantation is a research group that studies the implantation of animal organs into humans. Experiments in monkeys have shown that pigs like the pig kidneys received by brain-dead women can usually last a week without problems. Robert Montgomery, a surgeon at New York University, did not give an interview to Science, but at a news conference last month, he defended the study, noting that "there are many other examples of preclinical studies in primates that don't translate well into the human condition." ”
Lacking a sugar gene, these organs are not a viable option for xenotransplantation that will last for years. Other sugar molecules on pig cells have similar immune triggering effects, and experts say they should also be cleared by genes. In addition, some human genes may need to be added to the pig genome to further modulate the body's immune response. But the pigs were designed by a biotech company called Revivicor, and they do have the potential to reduce the chances of immune rejection in other medical applications. Thomas Platts Mills, a clinical immunologist at the University of Virginia, said: "Just removing a sugar makes a big difference. ”
For example, in the late 21st century, Platts Mills discovered that tick bites cause abnormal allergic reactions to alpha-gal. People with this "alpha-gal syndrome" (AGS) react severely to red meat and many livestock medical byproducts, including the blood thinner heparin (made from pig intestines) and implantable devices such as biological artificial heart valves for cattle or pigs. (The antibodies that cause these allergic reactions, caused only by tick bites, carry these antibodies in everyone, unlike those that attack transplanted pig organs.) ）
Revivicor received regulatory approval for its engineered pigs as a meat source in December 2020, and while pork chops and sausage pies for pigs aren't yet available, the company has begun sending free samples to people like Amber Shifflett of Charlotte Hall, Maryland, who have AGS and have spent months avoiding eating red meat. One Saturday in mid-October, Shifflett, 30, made a hypoallergenic ham steak for breakfast. Then she had another piece of ham steak for dinner. "I was nervous at first," Shifflett said. Will her breasts be as tight as they normally are after eating meat? Now, she says, "I'm fine, I just want to savor every bite." ”
In addition to meat, Scott Commins, an allergist who treats AGS at the University of North Carolina at Chapel Hill, wants to provide his patients with allergy-free medications. "Bacon is fine," Commins said, "but I really believe that animals have broader uses in medicine, which is arguably more important." "For example, during a pandemic, a safe heparin may benefit patients with AGS who have coagulation problems due to COVID-19.
Some medical products for pigs that do not contain α-gal can be used outside of AGS patients. For example, replacement heart valves are increasingly made of tissue from cattle and pigs, rather than mechanical substitutes. But partly due to immune attack, these bioprosthetic valves deteriorate and must be replaced after 10 to 15 years. To mitigate this attack, animal-derived valves are stripped of cellular material and chemically treated to mask immune stimulation residues. But according to Joseph Turek, a pediatric cardiac surgeon at Duke University, α-gal can still be detected at "actually quite amazing" levels, as he, Commins and others reported in the April Thoracic and Cardiovascular Surgery. Turek's research was funded in part by Revivico, who estimates that valves without α-gal may last twice as long as other biological prosthetic valves.
Pigs without α-gal can also serve as skin donors for burn patients, as well as as as a neuronal source for treating peripheral nerve damage. A company called Alexis Bio (formerly XenoTherapeutics) has tested pig skin on six patients with third-degree burns. Usually, doctors rely on dead people's skin as a temporary dressing until the patient can transplant their own skin. But cadaver skin is expensive and often in short supply. Engineered pig skin also appears to have helped wounds heal for up to 9 days, the longest duration assessed to date.
Jeremy Goverman, a burn surgeon and trial investigator at Massachusetts General Hospital (MGH), said, "The most striking thing about pig skin is that there is nothing striking about it. "Because the graft only stays in the body for a week or two, the immune system doesn't have time to reject it." Paul Holzer, CEO of Alexis Bio, said: "Its use is short-term. ”
His company and another startup, Axonova Medical, are also developing nerve transplants for the same breeding pigs. These could replace the current "preferred" approach to nerve repair surgery: the option of collecting nerves from other parts of the body, an option that is not always possible and can leave people with sensory problems.
Axonova's research director, Krika Katiyar, and her colleagues started with neurons in Revivicor pig embryos and cultured them into 5 centimeters of nerves. The company has repaired damaged leg nerves in mice and facial nerves in pigs, and plans to continue monkey research in the next step. Meanwhile, MGH plastic surgeons Curtis Cetrulo, Holzer and colleagues reported in September that they used the leg nerves of pigs missing alpha-gal to repair damaged arm nerves in rhesus monkeys. In the two teams' more than 6-month study, the recipient animals' own nerve cells replaced the pig tissue, eliminating the risk of immune rejection. Katiyar said: "It looks like the host tissue has taken over completely and the graft has been naturally removed from the body. ”
Researchers such as Christopher Burlak, a xenotransplant scientist at the University of Miami, are waiting for the day when larger organs — kidneys, livers or hearts — are transplanted from pigs to save lives. He said NYU research is "the first step on a long road." Companies are already working on the next step of research to design pig organ donors that remove three or more genes and add up to nine human genes. None of these pig organs have been tested on humans. "The next big advance in the field will be real transplantation," Burlak said, "rather than a short-term assessment of xenotransplantation in dead people." ”
Resources:
https://www.science.org/content/article/skin-nerve-transplants-genetically-modified-pigs-could-help-humans-organs-are-way
Note: This article is intended to introduce the progress of medical research and cannot be used as a reference for treatment options. For health guidance, please visit a regular hospital.
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