Unexpectedly, "Second Brother" is really a treasure boy.
It is reported that 20 people die every day while waiting for organ transplantation. The data shows that there are more than 1 13000 people waiting for transplantation in the United States, while there were only 36528 transplant operations in 20 18 years, and more and more people are waiting for transplantation every year, far exceeding the number of available organs. However, the progress of science and technology provides a glimmer of hope for solving this problem. Transgenic pigs may help mankind write a new chapter in medical achievements.
Grafton, Massachusetts is a small town about 40 miles west of Boston. There is a pathogen-free institution in the town, which is mainly responsible for cultivating experimental miniature pigs that provide human skin through genetic engineering.
The skin of these miniature pigs looks very similar to human skin and is called heterogeneous skin. To speed up the healing process, surgeons at Massachusetts General Hospital will transplant the skin of these pigs to a small group of burn patients. This is the first experiment approved by the US Food and Drug Administration to use living animal tissues in human body, and it is a necessary step to transplant the complete organs grown in animals to people in need. This process is called xenotransplantation.
As we all know, the demand for these organs is very urgent. Every day, 20 people die while waiting for organ transplantation. According to government data, there are currently more than 165438+3000 people waiting for transplantation in the United States, while there were only 36528 transplant operations in 20 18 years. Therefore, there are more and more people waiting for transplantation every year, far exceeding the number of organs available. For decades, researchers have regarded animal donors as one of the ways to alleviate this long-term shortage, but animal organ transplantation often fails.
It can be said that xenogenic skin developed by XenoTherapeutics, a biotechnology company headquartered in Boston, has broad prospects. So far, one patient has received transgenic pig skin transplantation, and another five burn patients are waiting for transplantation. These skins are only temporarily transplanted into the human body, and once the patient's skin grows out, it will be removed. The doctors who participated in the experiment said that the donor tissue seems to be healing, and the skin of the transplanted human body is also healing, and there is no rejection in this process, such as triggering an immune response or spreading animal viruses-these two problems are the main problems faced by xenotransplantation. Aul Holzer, CEO of XenoTherapeutics, told OneZero: "We are moving towards the goal of completely replicating the standard skin with severe and extensive burns."
Generally speaking, severe second and third degree burns will be treated with allogenic or human cadaveric skin. Allotransplantation helps to protect the wound from infection, prevent the loss of body fluids from the body and promote the regeneration of patients' skin. Dr Curtis Rullo, a plastic surgeon at Massachusetts General Hospital and former chairman of the board of XenoTherapeutics, said, "Skin is an important barrier to everything in the world. As human beings, we are like a bag of liquid and our skin is like a plastic bag. "
Because human skin can survive for some time after death, this is also the reason why it can be preserved in people and pigs and transplanted to patients. But like other organs, cadaver skin is expensive, and it is difficult to get it from the National Skin Bank because there are not enough donors. Skin banks have strict standards and cannot accept donor skin infected by cancer or viruses such as HIV and hepatitis, because these diseases may spread to transplant recipients. Some skin banks also have restrictions on the age of skin donors.
Holzer said that when there is a shortage of corpse skin-especially in the battlefield and developing countries-pigskin may be a substitute. The skin of pigs and other animals has been used as wound dressing, but these skins are chemically treated and dry, so there are no living cells in these skins. "It's basically like a piece of leather," Cetrulo said. "It's dead skin, not processed skin."
Heterogeneous skin is composed of living tissue, which aims to promote blood flow or blood vessel growth, which is a key step to help fight infection in the healing process. The first patient received a 5×5 cm xenograft skin, but subsequent patients will receive a larger area of transplantation. Five days after the first patient received the transplant, the surgeon took out the transplanted skin and replaced it with a permanent graft on the patient's thigh. At present, the patient is recovering and is expected to return to work soon.
In the long run, it is much easier to transplant pigskin to the burn site temporarily than to transplant pig organs into human body, but Dr. Abbas Ardehali, a heart-lung transplant surgeon at UCLA, said that it is meaningful to transplant pigskin to the burn site temporarily from the safety point of view. "I think the advantage of this method is that even in the worst case, such as pigskin failure, you can start all over again. It is not that a major operation like a heart or lung transplant is fatal once it fails. "
Scientists have been trying to transplant animal organs into human body for a long time, and heterogeneous skin is the latest experiment. In 1960s, American surgeon Keith Reemtsma transplanted chimpanzee kidneys into human body, but the experiment failed because of rejection or infection of these organs. 1984, a baby named "Baby Fae" received a heart transplant from a baboon, but died within one month.
Although apes and monkeys are our close relatives, scientists now think that pigs are ideal providers of human organs. To a large extent, the reasons are as follows: First, it takes only a few months for a pig's organ to grow to a suitable size, while it takes 10 to 15 years for a monkey. In addition, pig organs are closer to human organs. At the same time, the National Institutes of Health has terminated its research on chimpanzees. Scientists believe that compared with monkeys, the public may be more morally receptive to using pigs as organ donors, because the public has become accustomed to the role of pigs in agriculture.
However, the biological differences between pigs and humans make transplant rejection a big problem for scientists. At present, scientists are committed to using genetic engineering to solve this problem. In the 1990s, Dr. David Sachs of Massachusetts General Hospital used genetic engineering technology to eliminate a molecule called α-gal found in pigs, which would trigger an immune system response. This single genetic modification may make the human body no longer reject small and temporary pig skin transplantation. However, in order to ensure that the whole transplanted organ can survive in the human body for many years, researchers may need to make more changes to the pig genome and develop new immunosuppressive drugs for transplant recipients.
In 20 16, researchers from the National Institutes of Health, led by Dr. Mohammed Mohiuddin, reported that they transplanted the heart of transgenic pigs into baboons, and the average survival time was over one year. One of the baboons lived for more than two and a half years, breaking the previous record of heart transplantation from pigs to primates.
The gene editing tool CRISPR can also easily modify animals for xenotransplantation. In 20 17, a startup company named eGenesis announced that it had successfully eliminated a group of viruses found only in pigs, which have long been considered to cause human infection risk when accepting pig organ transplantation. Porcine endogenous retrovirus is considered to be another major obstacle to human organ transplantation. Although no one has been infected with PERV due to transplantation, laboratory research has not yet reached a conclusion.
Dr. Megan Sykes, director of the Center for Translational Immunology at Columbia University, said: "At present, most people in the xenotransplantation community claim that the risk is controllable. The fact that the Food and Drug Administration approved this experiment also reflects this idea. "
Like their "predecessors", pigs used for heterogeneous skin research must first be genetically engineered to prevent transplant rejection. But it may take several years to see the first pig organ transplanted into human body.
"We must ensure the success of skin or other non-lethal tissue transplantation," Ardehali said. "Next, we can try the kidney, because if the kidney fails, the patient can still live on dialysis, but if the heart or lung fails, I'm afraid God can't save you."
However, even if the technical problems are solved, persuading the public to accept pig organ transplantation may be a very big problem. Mohiuddin is now the director of the heart transplant program at the University of Maryland School of Medicine. He said that although xenotransplantation has broad prospects and great potential, changing public opinion may be a long-term process.
Mohiuddin said: "If you tell others,' We want to implant a pig's heart into your body', it may cause an uproar. If the trial is successful, it will pave the way for other types of transplants, such as kidneys, hearts, lungs or livers. "
One of the initial uses of organ xenotransplantation may be so-called bridge transplantation, that is, patients need an organ to maintain their lives for a period of time, such as weeks or even months, until they can get a more suitable organ from a human donor. Mohiuddin said: "But I believe that once we have an ideal pig donor and the organs they provide can live longer, we don't need to replace new human organs."
At the same time, XenoTherapeutics is also cultivating the nerves of transgenic pigs, which can be transplanted to people whose nerves are damaged by car accidents, falls or other reasons. The company hopes to start clinical trials of this method in 2020.
Ardehali said that in the next five to 10 years, people who need organ transplants are still unlikely to choose to transplant pig hearts or lungs, but he does think that this situation is getting closer.
He said: "We have maintained great enthusiasm for many years, but this has not really become a reality. Are we writing a new chapter in the history of human medicine? I don't know, but it actually requires a major leap in faith. "
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