Jiangsu was born the first batch of "high price" transgenic clone pigs

Nanjing Medical University announced yesterday that the first batch of (4) genetically modified cloned pigs was born at its experimental base in Jiangning. This is the first batch of research results since the establishment of the Key Laboratory of Xenotransplantation in Jiangsu Province in August this year. At present, the piglets are in good health.

These four little guys are the first genetically modified clone pigs in Jiangsu, and the islet system on this kind of pig will probably help people solve their diabetes for the rest of their lives. Yesterday, Modern Express reporter interviewed Dai Yifan, deputy director of the Metabolic Disease Research Center of Nanjing Medical University. He is also one of the leaders of the transgenic cloning pig project. Dai Yifan calmly stated: "The ultimate goal of our scientific research is to develop human usable organs in pigs, and now is only the first step."

Remove one gene and then “generate” the genes

Strictly speaking, genetically modified cloned pigs have neither "dad" nor "mother". Where did they come from?

In early 2011, Professor Dai Yifan brought dozens of cells from the United States to Nanjing with "knockout pigs." These are the cells of genetically engineered pigs. Thousands of pigs can be cloned from each tube. From June this year, laboratory workers started to welcome the birth of pigs. What we get back is just the "formula" of cells. We need to do further genetic transformation. First remove some of the cell's genes (α-GAL), and then “plant” a special gene (hCD46) to grow pigs through somatic cell cloning. After the completion of the laboratory phase, the staff selected a farm in Jiangning and selected a "surrogate mother" for the cells. Researcher Li Rongfeng revealed: “After 114 days of pregnancy, the sow began production on October 13 this year. After the piglet was born, it was mainly relying on the sow’s breastfeeding.” The four sows look cute, but the difference in weight is very high. The largest and the smallest are only 370 grams, and the largest is more than 1,100 grams. "If you are light, you have to be weak. We need extra care." In the first half of last year, Dai Yifan and other experts had already cultivated the first batch of boars in Guangzhou. Experts revealed: “At present, the first batch of young boars has matured and averaged two or three hundred pounds. It will be brought back to Jiangsu in the future. For future mating and breeding, this batch of piglets is all female.”

Genetically modified pigs are similar to normal pigs in terms of appearance, breeding, and reproduction. By the second generation, the pigs can be naturally produced and naturally fed just like ordinary pigs. This means that soon, the pigs can be “dad” or “mother”. "Actually, when I was doing research in the United States, I had already cloned similar pigs. After more than 10 years, it was very good to grow and reproduce." Dai Yifan revealed: "Now the doctors of Nanyi Medical University are very popular, both at home and abroad. Have come to talk about cooperation."

In the United States, genetically modified pigs are known as "million-dollar pigs". Is it really so expensive? Dai Yifan said with a smile: This is to say that we have spent so much money to cultivate the first genetically modified pig. We need to use cloning technology to add genes or knock out genes in cells. After the birth of the first-generation pig, the cost will be reduced because a large number of genetically modified pigs can be cultivated through natural breeding. "So we have to take care of this first-generation pig, otherwise if someone takes away their own breeding, then the loss can be big."

The appearance is not amazing, but it is a million dollars baby

This pig has a good use

Can transplant human islets

Experts revealed that the transplantation of islets of transgenic pigs to monkeys has a wonderful effect. “We did experiments abroad. After the transplant, the monkeys got better with diabetes without any insulin injection because the islets of the pigs had a role in the monkeys and the monkeys that received the islet transplant survived for more than 400 days. Diabetes patients either take medicine to control blood sugar or have a lifetime of insulin injection. The patient is very painful. If a whole set of islet system can be transplanted into the human body, it will completely solve the problem of diabetes."

If the pig's organs are moved into the human body, the pigs who must provide the donor must be absolutely clean, so a super-clean pig farm must be provided. The pighouse must be completely free of bacteria and viruses. Feed and water must also be sterile and non-toxic. “With a super hog farm, we can even make the pig’s organs even cleaner than human organs because we can eliminate all viruses.” Professor Dai Yifan will build such an “ultra-clean pig farm” in Hengxi, Jiangning. ", breeding 5000-10000 such pigs. The "second-generation pigs" undergo caesarean section and are separated from their mothers immediately after they are born. The artificial feeding is carried out in a sterile environment. Through a series of quarantine standards during the rearing process, such pigs and their organs can be used clinically. For more clinical requirements, in order to make the pig cleaner, the adverse impact on the human body is reduced to a lower level. "The third generation of pigs must be able to provide organs."

It is reported that ultra-clean pig farms in Jiangning are expected to be built in 2014-2015. The fastest possible clinical studies will be conducted in 2017. They are used on humans. “Of course, this refers to scientific research, and it really needs large-scale clinical promotion. a long time."

Two interesting questions

For the transformation of genes?

For organ transplantation does not exclude

In Dai Yifan's eyes, the pig may be the "universal pig" that is needed for future human organ transplantation. "It's like a person with type O blood can give blood to everyone, just like a pig that has knocked out its genes, its organs have become 'O' organs that can be transplanted to anyone, and super-acute row will hardly happen. I'm different," Dai Yifan explained in a GM pig.

The data shows that there are 1.5 million patients in need of transplanted organs every year in our country, but less than 10,000 patients are finally able to obtain donors and receive transplants. If the pig's organs can be transplanted to humans, it will undoubtedly be the hope of many terminally ill patients.

Dai Yifan said that in the past, scientists had directly “grafted” pig organs onto the human body and the result failed. why? This is because pigs have a gene α-GT (galactosyltransferase gene) that is not found in primates and its product α-GAL sugar molecules are similar to human blood group molecules and are pig's organs. The main source of strong rejection in monkeys or humans. Dai Yifan’s research team is using molecular biology techniques and cloning pig technology to remove the α-GAL gene from pigs and breed genetically engineered pigs to overcome the problem of hyperacute rejection of pig organs by monkeys and humans. , thus taking a key step in the compatibility of porcine organs with the human body. “It was later discovered that the islets of the cloned pigs that had been genetically modified with hCD46 had a good effect on the islets, so the pigs were first bred.”

Why choose pigs?

Low cost and not easy to infect

It is well-known that the closest kinship to humans is primates, such as monkeys, orangutans, and baboons. Then why do we choose pigs for human patients?

Dai Yifan said with a smile that monkeys and other animals have a slow growth cycle (usually 5 to 10 years or even more than 10 years), and they have a low reproductive rate, a single child, a baby, and a high feeding cost, and it is difficult to meet the needs of human organ transplantation. . In addition, such animals, such as monkeys, are small in size and light in weight, and their organs are not suitable for many people. "People like me who weigh, if they do liver transplants, I am afraid that a monkey is not enough." Another important reason is that primates and humans are closer, many viruses and humans cross-infection, such as AIDS HIV; some Viruses may also hybridize with human viruses and produce new viruses. There are serious security risks.

The pig is just the opposite. First of all, the growth cycle of pigs is very short, and one child has more production, lower feeding costs, and relatively easy access to organs. Second, in terms of shape and size, its organs can basically be applied to humans. Third, pigs are omnivores. Its organ metabolism is very close to that of humans. Therefore, its organs can be widely used as transplants for human cornea, skin, islets, joints, tendons, ligaments, kidneys, heart, and liver. Finally, the virus in pig tissue is less likely to infect humans.

final goal

Customize human organs on pigs

Not long ago, the British John B. Gordon and Japanese Yasuhiro Yamamoto won the 2012 Nobel Prize in Medicine for their cell research. The two winners found that the specialized cells that matured in the organism could be returned to the initial state by “reprogramming” and then modified and developed into any kind of cells. This is an epoch-making result that is expected to be applied to regenerative medicine and pharmaceuticals. Dai Yifan disclosed that in fact, "knockout genetic pigs" and this scientific research result are likely to be combined together in the future.

He disclosed that: "I have an idea to study the "humanized" or even "individualized" genetically modified pigs by placing individual stem cells in pig embryos and directing them to differentiate into an organ. " "Customized" can be used exclusively for most people or for organ transplants. Strictly speaking, this 'humanized' organ is not a pig's organ but a human organ."

According to the current situation, it is almost impossible to use stem cells to cultivate the necessary organs in vitro. However, experiments have been made in the world to prove that mice can also grow rat pancreas. Therefore, in theory, this concept is entirely feasible and pigs may grow human organs. But to really implement this idea, you need to do a lot of experiments to verify.

dialogue

Many people are concerned that when can pig organs cure diseases?

Dai Yifan: I received a large number of telephone calls. Many people asked if it was a pig organ that could cure people immediately. In fact, it was not that great. At present, the research and development of genetically modified pigs used in all kinds of organ transplants are still underway, because the requirements for various organs are different, and the degree of genetic modification is also different. For some organs without blood vessels, such as islets, corneas and other organs may carry out clinical research in advance, these organ transplantation rejection is small, but even so, it is only research. The real transplant of the liver and kidney organs has not yet reached the clinical stage, let alone treatment. Research has been done abroad, transplanting the kidneys of “knockout genetic pigs” to monkeys. The first two weeks were very good, but after the occurrence of thrombocytopenia, it quickly failed. This shows that after the super-rejection, there is some acute rejection of the transplant of the large organs, which may require us to continue genetic modification and modification of the pig until the final transformation is perfect. Scientific research is such that after discovering the first step, there are still many unknown scientific secrets waiting for us to crack.

Is it acceptable for all pigs to be transplanted onto the human body?

Dai Yifan: The first hand transplant in the world was in Australia. There was a patient who had no hands. The doctor then transplanted the donors of both hands to him. But when the patient sees the hands every day, he thinks of the donor. Serious psychological disorder, later the patient refused to eat anti-rejection drugs and lost his hands again. But the two-handed transplantation is only to improve the patient's life, not to save lives. For those who really need the help of the donor, it is certainly acceptable. To give a good example, there are no problems in human-to-human kidney, liver, heart, or lung transplantation. The reason is that, first of all, these donors are used to save lives, and secondly, these donors are transplanted into the body. missing. Therefore, whether to accept the organs of pigs as donors is entirely based on the actual conditions of the patients. Moreover, upon reaching the clinical stage, relevant experts will conduct research and verification on many issues. Excessive consideration of the many disputes that currently exist does not seem necessary.

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