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Japanese scientists mass-produce transgenic pigs Organs can be transplanted to humans

British media said that in the near future, we may be able to rely on pigs to carry out life-saving organ transplantation.
According to a report on the British “Daily Mail” website on March 8, a team of Japanese scientists said that they have already cultivated pigs that have genetically modified organs that can be transplanted to humans.

It is reported that these pigs were the first animals to be cultured for xenotransplantation. Xenotransplantation refers to the successful transplantation of animal organs and tissues into humans.

According to the Japan’s “Yomiuri Shimbun” report, the team includes researchers from Meiji University and Kyoto Prefectural University, who hope to provide these pigs to a private company early next year.

It has been found that pigs are ideal objects for studying how to treat or prevent certain human diseases.
The leader of this research, Meiji University’s Professor Naoji Luizhi, spent several years studying transgenic pigs as a model of human genetic disease.

Now he has developed a way to grow organs that can be transplanted into the body in pigs.

According to the report, scientists first collected induced pluripotent stem cells from a patient and injected these human stem cells into “custom” pig embryos. These embryos had previously been genetically modified and did not have the ability to grow out of the pancreas.
The study stated: “This creates a ‘gap’ or ‘space’ that can be occupied later.”

Subsequently, stem cells enable human organs to grow in porcine embryos.
Although the study focused on creating the pancreas, scientists said that this process may be applicable to many different organs.

Reported that before the sows gave birth, the scientists removed the uterus and removed the piglets in a pathogen-free room.

The scientists obtained a total of 17 piglets.
They fed the piglets with sterile artificial milk and raised them for about a month.

Scientists must adhere to strict safety and health guidelines when implementing artificial reproduction techniques.
According to the Yomiuri Shimbun, some guidelines require that pigs be kept in a clean and protected environment. 40 viruses should be tested to prevent infection and ensure patient safety.

They hope that pigs can save those who suffer from organ failure and cannot find transplant organs.
Long Island than Lu Zhi said: “In the near future, patients do not have to wait.”

The Joint Organisation of Organisation of Organ Sharing said that on average, 20 Americans die each day while waiting for an organ transplant.
Reported that for more than a decade, scientists have been studying how to use the “model animal” with a transplantable organ to save human life.

In addition to cultivating animals used for organ transplants, Nagashima Tokihiro “borrowed the body of pigs” to study hereditary human diseases, including diabetes, amyotrophic lateral sclerosis (commonly known as degenerative frost), hereditary metabolic disorders, and muscles. Malnutrition and so on.

Longlu Zhilu explained: “I believe that the disease model pigs we have developed are very useful for the development of therapies and drugs for these patients.”

He also said: “My dream is to see with my own eyes that some patients are cured through our therapy.”
According to reports, pig-to-human xenotransplantation has been carried out in countries such as New Zealand and Russia. However, this practice has also been opposed by some scientists and bioethics scientists who believe that inter-species embryos “are detrimental to our humanity.”

The report said that despite this, the National Institutes of Health in 2016 suspended the suspension of funding for these controversial experiments. This means that scientists can use federal government funds to make transgenic embryos under certain closely monitored conditions. This kind of embryo is also called a chimera.



Harvard University and other research institutes and company teams use the CRISPR-Cas9 gene editing technology to eliminate the endogenous retrovirus (PERV) contained in the pig genome, which is considered as a major breakthrough in the use of pig organs for human transplantation. .

The removal of PERV may solve two problems. First, if the pig organ can be transplanted into the human body, the risk that the virus may cause people to be infected is ruled out. Second, the immune rejection after the organ transplant that the virus may cause is eliminated.
Transplanting animal organs to humans is a heterogeneous (peace) transplant that is significantly more complex than adopting human organs (allogeneic homografts) and has more technical challenges. Although this is an aspect, it is far better than using human organs for transplantation, and it can only be a record or spare tire.

According to the principle of “Road to Rome”, on the one hand, it is explored as a path of organ transplantation. On the other hand, it focuses on transplanting human organs. At present, it mainly encourages more people to die. Donate organs afterwards.

Even if the pig’s PERV is cut off, the problems of safety and rejection still exist, and it is obviously more than that of transplanting human organs. Because it is a heterogeneous organ, there are many more immunogenic substances (molecules) on the pig’s organs that can trigger immune reactions, and many problems such as immune rejection need to be resolved.

In addition, because it is a xenobiotic organ, the life span of the pig and the physiological functions of the organ are also different from those of humans, which may make it difficult to ensure that the organ transplanted to the pig has the same physiological functions as the human organ.

At present, the longest survivors of human liver transplants have surpassed 33 years, and kidney transplant recipients can survive longer. The longest survival time of living kidney transplant patients in the world is nearly 40 years (non-relative donor kidneys in China The maximum survival period for transplantation is 27 years). Measured only by the number of years of survival, it would have to be several times more than transplanting human organs, which obviously would create more insecurity.

In addition, because of the heterogeneous organs, the dose of anti-immune rejection drugs taken after the rejection reaction may be very large, which may affect the quality of life of the recipient and the life span of the recipient.

The greatest motivation for using animal organs for transplantation is to solve the problem of organ supply. If we can solve this problem, it is clear that adopting human organs is not only safer and more durable, but also ethically safer for recipients, at least not to worry that it is a human face. “Or “pig heart dog lung.”

No matter whether in China or in other countries of the world, the technology of organ transplantation is not a problem. The biggest problem is the rate of organ donation, and it also determines how many people’s lives can be saved by organ transplantation. Organ donation rate refers to the total number of organ donations in a country divided by the number of people in the country, that is, how many people per million people donate organs.

According to statistics from the World Health Organization’s Global Donation and Transplantation Observatory in 2016, the highest global donation rate is in Spain, at 43.8%; the United States is fifth, at 30.76%; China ranks 51, at 2.98%.

The National Conference on Human Organ Donation and Transplantation in 2017 revealed that nearly 300,000 volunteers for human organ donation have been registered in China, and over 12,000 cases of organ donation have been completed, and more than 34,500 large organs have been donated. At present, the number of donated human organs and the number of transplants are both ranked second in the world. However, the donation rate is also ranked behind. If the donation rate can be increased, human donor organs can fully meet the needs of organ transplantation.

Resolving this issue requires addressing why the Chinese don’t want to donate organs. A survey in 2011 showed that the highest proportion of all cadaveric remains was 33.1% after death, fearing that donated organs would cause organ sales of up to 30.1%; organ donation is not enough to know about organ donation That’s 20.69%; only 1% think it’s unnecessary to help others.

Therefore, by addressing the first three factors, China’s donor organs can meet demand. In the past two years, China has done a great deal of work on the fear of organ donation that causes the sale of organs. It has abolished the death of organ transplant recipients and increased the rate of organ donation.

Of course, this does not mean that the transplantation of animal organs for humans is not worth studying. If there is also a full-scale breakthrough in this respect, it will be a powerful supplement to organ transplantation.

Researchers from the United States, China and Denmark announced on the 10th that they have cultivated the world’s first live pigs that are not “toxic” to organ transplants and successfully solved the most important safety issues in the use of pig organs for human transplants. Millions of patients with organ transplants bring hope.

The research team led by eGenesis Inc. of the United States published thesis in the American academic journal “Science” on the same day. Harvard Medical School, China Yunnan Agricultural University and Aarhus University of Denmark were also involved in the research.

“Our work has fundamentally solved the risk of heterologous virus transmission in xenotransplantation,” said Yang Xin, co-founder and Chief Scientific Officer of eGenesis, who told Xinhua News Agency reporters. “The pigs are a groundbreaking breed of pigs. In the future, xenotransplantation is expected to be safely applied clinically.”

According to incomplete statistics, about 2 million people in the world need organ transplants, but the number of organ donations is much lower than demand. Porcine organs are considered to be suitable for transplantation due to their similarity in size and function to human organs.

In the 1990s, scientists tried xenotransplantation. However, experiments have found that pig organs contain not only immunological problems but also “poisonous” in the human body because the pig genome contains an endogenous retrovirus. In the end, both the World Health Organization and the U.S. government have explicitly ordered that all clinical trials of xenotransplantation be stopped before a solution is found, and the xenotransplantation industry has stagnated for many years.

In 2015, Dr. Yang, who was a postdoctoral fellow at Harvard University, successfully knocked out all potentially harmful viral genes in the pig genome with the aid of the gene editing tool CRISPR. This breakthrough was the first major breakthrough in vitro.

In the latest study, Yang Hao and others used CRISPR tools and small molecule drugs to successfully modify the 25 gene loci in the pig’s primary fibroblast genome. Then, like cultivating the world’s first somatic cell clone animal “Dolly” sheep, the researchers used a modified porcine fiber cell to create pig embryos and transplanted them into sows. Endogenous retrovirus inactivated pigs.

“At least in their 4 months of age, we did not observe a physiological difference between the modified pig and the normal piglet,” Yang said. “We will continue to reform the genome to solve the problem on the basis of these pig breeds.” Exclude the issue, strive to realize the clinical application of xenotransplantation as soon as possible, and save thousands of patients waiting for organ transplant.”

Darren Griffin, a professor at the University of Kent in the United Kingdom, commented that this work is a “major step” towards the realization of xenotransplantation. But he also cautioned that there are many variables in this area that include ethical issues that need to be addressed.

Professor Ian McConnell of Cambridge University in the United Kingdom also commented that this is a “first step full of hope”, but the development of xenotransplantation remains to be seen, because even if the problem of heterologous virus transmission is solved, it must be overcome. There are numerous obstacles such as immune rejection and physiological incompatibility of pig organs in the human body.