Following the world's first human transplant of pig heart, the United States completed the second and third similar surgeries in the world in June and July this year.
The surgery was completed by the NYU Langone Medical Center team at New York University in the United States, and three important endpoints were achieved: First, the transplanted pig heart functioned. Second, within 72 hours after the operation, the two transplantees did not experience rejection. Third, cardiac biopsies and the like did not detect porcine CYTOV.
01 Two pig hearts were successfully transplanted in brain dead patients
In January this year, the University of Maryland Medical Center in the United States completed the world's first pig heart transplant, which attracted widespread attention. Patient Bennett, a 57-year-old man with heart disease, performed well for several weeks after the transplant without any signs of rejection. However, the patient died just two months after the operation, the reason was unknown at the time, and in May the MIT Technology Review reported that transplant experts said that a swine virus carried by the pig heart may have caused the patient's condition to worsen.
The most recent study, led by NYU Langone expert Nader Moazami, involved two patients from Pennsylvania, a Vietnam Veteran with a long-term heart attack, and New York, a woman who had also received an organ transplant before, both of whom had been pronounced brain dead before the transplant and had been ventilated and undergone dialysis before, during and after surgery. The team conducted intensive testing for 3 days after the operation, frequently checking the condition of the pig's heart, and finally the doctor turned off the life support device and let the test officially end.
The surgical team adopted the usual method of heart transplantation, first growing 10 genetically modified pigs in a specific environment, 4 genes that increased the risk of transplant rejection and abnormal organ growth were turned off, while another 6 inserted human genes reduced the incompatibility between the pig and the human biological pathway. The desired heart of the pig is frozen and transported by plane to New York, hundreds of miles away.
Unlike the world's first pig heart transplant completed by the University of Maryland Medical Center in the United States, NYU Langone has made many "new attempts":
First, when transporting pig hearts, only portable organ maintenance systems are used. The pig heart comes from Revivicor Company in Virginia, USA, and the pig heart used in the world's first pig heart transplant is also from the same donor pig of the company. Preoperative researchers go to the company, obtain pig hearts, and put them into a preservation solution and place them in a portable organ maintenance system.
Second, develop targeted porcine virus detection methods. Sapna Mehta, director of NYU's Transplant Infectious Diseases Program and clinical director at NYU's Langone Transplant Institute, called the method "more sensitive" and suitable for both pig heart donors and transplantees. The details have not yet been announced.
Third, streamline the operation and achieve time reduction. Postoperative researchers also provided patients with standard post-transplant medications to suppress the immune response.
Nada Mozami said he stood there in awe when he saw the pig's heart beating in the human body.
Robert Montgomery, director of the Langone Transplant Institute at New York University, said: "Seeing a pig's heart beating and working in a human chest is one of the most incredible things, and it is a great honor to witness it all in my lifetime." "It's a whole new field!"
02The high imitation lock of the key to life, can the corpse open the way for living transplantation?
The high imitation lock, which can be called the key to life, provides a promising solution to the shortage of donor organs.
In the United States alone, more than 105,000 people are waiting for an organ transplant, and an average of 17 people die every day without waiting for a suitable transplant. China currently registers about 300,000 people in need of organ transplants, but only about 16,000 organs are successfully transplanted each year, so the shortage of transplanted organs has led scientists to boldly think of xenotransplantation.
However, whether the original key can be equipped with a "high imitation lock" lies in whether it can solve the transplant rejection reaction of using animal organs. Because the immune system attacks transplanted organs, it eventually leads to organ failure.
"During the observation period, the transplanted hearts of the two subjects functioned normally and there was no rejection. We believe that the problem of ultra-acute rejection has been solved through technologies such as donor pig gene editing. At the same time, we captured everything that happened in real time within 72 hours, and we went deep into the internal organization of the body to observe, and the information obtained was very large. NYU Langone press release shows.
David Klassen, an expert at the Nonprofit United Network for Organ Sharing, said testing on the dead is an important stepping stone to help researchers fine-tune the operation of different steps before living human trials. He suggested that this time the New York researchers extend the test time from 3 days to about 1 week.
Some scholars believe that there is an essential difference between the living and the corpse. After brain death, although the body's circulatory system can be maintained, the specific functions of endocrine and organs will undergo different changes. The results of the study at this time may not be applicable to normal human bodies.
And some viruses are endogenously embedded in pig genes, in the carcass, many enzymes and other related factors are inhibited, and may be activated and expressed in the living.
A few months ago, researchers at New York University and the University of Alabama in Birmingham also tested pig kidney transplants on the deceased. Montgomery, a kidney transplant surgeon at NYU Langone Medical Center, said testing on the deceased is not life-threatening and helps to learn and find the best solution.
The U.S. FDA is considering whether to approve a small number of patients who need transplants to voluntarily undergo swine organ research, and New York University Langone Medical Center, one of three trial centers, is scheduled to discuss trial conditions with the FDA next month.
03 The development and hope of xenotransplantation
Based on a brief history of the development of xenotransplantation, we can learn:
As early as 1902-1923, human xenotransplantation attempts were carried out from pig, sheep and monkey organs, all of which ended in failure;
In 1963, baboon-derived kidney transplantation helped patients survive for 19-98 days; A chimpanzee-derived kidney transplant helped one patient survive for 9 months, but the other 12 patients who were performed at the same time were not so lucky, but this attempt encouraged visceral transplantation;
In 1964, after the first heart transplant of mammalian origin, the patient survived for only 2 hours;
In 1983, a newborn survived 20 days after receiving a heart transplant of baboon origin;
In 1995, an HIV patient received a baboon bone marrow transplant but died 2 weeks later;
In 1996, swine cell transplantation was used to treat diabetes;
In 1997, due to ethical issues and protests by the Animal Protection Society, any institution was banned worldwide from performing xenotransplantation;
In 2000-2011, regulations were issued in some parts of the world to allow for xenotransplantation studies.
……
However, at present, there is no xenotransplantation technology that has been licensed for application, and several basic problems need to be solved in order to achieve xenotransplantation. The first is the problem of immune rejection, organ transplantation between humans and people will still occur immune rejection, not to mention cross-species, strong immune rejection makes people die faster. Secondly, the humanization process is also a difficult point, otherwise there may be problems with the organ itself after xenotransplantation, or the transplant is just a piece of meat.
And why can pigs be transplant donors? As a "close relative" on the evolutionary tree, pigs have contributed many organ and tissue transplant sources to humans - from the earliest pig heart valves, to the later pig skin transplantation treatment burns, pig bone transplantation for bone defects, and pig corneal transplantation for blindness, all of which have entered clinical applications.
Most of these "contributed" things are relatively simple in structure, replaced by physical structures, and their functional cells are basically not involved in the body's important metabolism, or the cell surface glycosaline proteins that trigger various rejection reactions are easier to elute. But the visceral system is too complex, so there has been little progress in transplantation in this area.
In addition to xenotransplantation, organ transplantation also has other ideas:
Stem cell technology: Promising technology, but it is not yet possible to grow stem cells into organs.
3D printing technology: What needs to be solved now is how to make an organ as biologically active as possible. Although it has been achieved that the lungs can have a certain degree of autonomy, or the heart can beat, but it is still very far from organ transplantation.
Organ cloning: In fact, cloning is the most ideal way, many people want to grow organs with their own cells, but at present we do not have the ability to clone an organ alone. One strategy is to clone to embryonic stage to development and then take organs, however, which is unethical.
In this way, heterogeneous organs are still a realistic and feasible strategy, which is itself derived from living organs of animals, and can be clinically transplanted and survived.
Modern medicine has advanced rapidly, but how long will it take for xenotransplantation to be used in the clinic in the future, and we still need to explore this road for a long time. Some people joke that they have waited until the matching organs, and the xenotransplantation technology will not come. The latest progress in pig heart transplantation has brought us new expectations, and we also expect more cases to help us crack xenotransplantation. Secondly, it is also necessary to continuously improve auxiliary technologies such as anesthesia, critical care medicine, testing, imaging, blood transfusion, and nursing.
This article is derived from Huihui Medicine Cafe