Tide Sound Writing Zhang Miao Ding Shan Chen Xiao It is foreseeable that the meaning of the idioms of "human face and beast heart" and "wolf heart and dog lungs" will soon change - not long ago, the research team of the University Hospital of Munich, Germany, told ** that the research on human transplantation of pig hearts is in the "final sprint stage", and it is estimated that it can be put into application in two years.
China, which is in the first echelon of xenotransplantation, is also waiting for a breakthrough in the critical point of clinical trials. Going to southwest China, Chao News reporters saw the plot of science fiction shining into reality in the country's largest gene-edited pig breeding center in Neijiang, Sichuan; Walking into the northwest, Chao News reporters witnessed their exploration of the mystery of life in the transplant team of academician Dou Kefeng of the First Affiliated Hospital of the Air Force Military Medical University (Xijing Hospital) in Xi'an.
Gene-edited pigs sent to Xijing Hospital.
Another pressing reality is that 300,000 organ failure patients in China need transplants every year, and due to the severe shortage of organ resources, only more than 20,000 transplants can be completed each year, with an organ donation rate (PMP) of 3 per million populationThe number 73 is far from sufficient.
Pig organs, can they really save their lives?
Why are pig organs better suited for transplantation into humans than primates?
Dou Kefeng, an academician of the Chinese Academy of Sciences and a professor of hepatobiliary surgery at Xijing Hospital, has an entire wall of books in his office, and most of the books written in Chinese and English bring together the most exquisite results of organ transplantation, which is known as the "crown jewel of the surgical kingdom", and the difficulty of cross-species xenotransplantation has increased exponentially.
The rudiments of xenotransplantation predate even homogeneous transplantation, and in 17th-century France, a 15-year-old boy with severe fever and severe ischemia received an injection of fresh lamb's blood; After that, the transplant donors ranged from sheep, baboons to chimpanzees and other primates, and the transplanted organs studied included **, kidney, liver, heart, but due to technical limitations, the transplantation ended in failure; The failure of 4 xenotransplantation cases that occurred in the 80s and 90s of the last century made the clinical application of xenotransplantation directly banned.
Until the development of cloning technology and gene editing technology, as well as the advancement of allotransplantation technology, xenotransplantation finally completed the reserve of the underlying technology, and there were two breakthroughs in the past 2022: in January, a 57-year-old American patient with severe heart disease underwent a pig heart transplant and survived for 60 days; In October, Xijing Hospital transplanted six organs and tissues from a domestic gene-edited pig from four rhesus monkeys, which was the first in the world to be transplanted with xenogeneous organs.
In October last year, Academician Dou Kefeng (second from right) split the liver of gene-edited pigs ex vivo and took a suitable volume of part of the donor liver for xeno-assisted liver transplantation.
In the gene editing pig breeding center of Zhongke Aoge Biotechnology in Neijiang, Sichuan, in the exhibition hall, the model of the piglet, as an internationally recognized high-quality organ donor, the "second brother" is in the medical community to gradually defeat a variety of primates - their organ size, short gestational period, large number of litters, suitable gene editing tools, more importantly, the "second brother" does not have a major ethical problem like primates, and the 80 million years of kinship gap is far enough, there is a lower risk of zoonotic diseases.
Chinese doctors and scientists have seen the brightest biomedical light of all mankind in academic studies and international conferences, but the threshold of this hall is much higher than expected.
In 2010, the United States carried out a xenotransplantation operation, transplanting the liver of a pig into a monkey in its entirety, at that time we had mastered the mature homogeneous liver transplant surgery technology, and also wanted to carry out xenotransplantation research, contacted the team in the United States, only to learn that this genetically edited pig specially bred for xenotransplantation could not be exported. "Dou Kefeng knows very well that without gene-edited pigs, no matter how good the transplantation technology is, it will become a rice cook.
This field, which involves many disciplines such as molecular biology, cloning technology, biopharmaceuticals, transplant surgery, ethics, etc., is also a battlefield for great power rivalry, and if the key technologies are controlled by others, China's xenotransplantation research will not be able to advance.
It wasn't until 2013 that Dou Kefeng and his team performed China's first xenotransplant, "Any technique that may seem incredible yesterday may seem like a grudge today, but tomorrow it may become the norm." We believe that xenotransplantation will go clinically. At an international hepatobiliary and pancreatic surgery summit forum in 2016, Dou Kefeng, who served as a guest speaker, quoted this sentence from Stazel, the father of transplantation in the world.
How will a pig save hundreds of thousands of humans every year? In this discipline, which is only one foot away, it took China 10 years to enter the first echelon of xenotransplantation where the United States and Germany are located.
The life of a genetically edited piglet
In the southeast of Chengdu City, after a two-hour drive, the Chao News reporter entered a mountain village far away from the city and the factory, where the country's largest gene-edited pig breeding center is located.
Unlike the "compatriots" who are treated as pigs, the piglets here are destined to contribute organs from birth, and how is it different in their lives?
In October last year, two gene-edited pigs sat on the medical vehicle for full safety monitoring, starting from here, all the way to Xi'an, 800 kilometers away, in Xijing Hospital, one of the pigs' heart, liver, kidneys, cornea, ** cartilage was transplanted into 4 rhesus monkeys, it was recorded in the history of human medicine, and the other "accompanied" piglet is still living in Xijing Hospital.
Let's take a look at the baby pig first! "The person in charge of the gene editing pig breeding center of Zhongke Aoge Biotechnology ***, brought the tide news reporter to the big screen of the exhibition hall - without two showers and disinfection and 72 hours of isolation, we can't observe them in the pigsty at close range - seven or eight windows record the dynamics of different pig houses in real time. Focusing on one of them, a white pig is lying on the ground, and the round, soft and cute piglets are lying in a row next to them**, they have just been born for a month.
The more I looked, the more I wondered. The little pig is very similar to Jinhua's two black heads, with a black head and tail, and it looks different from the white mother pig. "The big white pig is the '** mother', and the little pig is the gene-edited Guangxi Bama pig. "* said.
Neijiang, Sichuan, the gene-edited piglets in the gene-edited pig breeding center of Zhongke Aoge Biotechnology.
Why Guangxi Parmesan pig? They weigh 30-50 kilograms as adults, which is similar to that of humans, and their organs are the same or similar in size.
In the homogeneous transplantation between people, "immune rejection" has always been a thorny problem, in order to make the pig's organs work normally in the human body, it is necessary to intervene at the beginning of the piglet's life - first, isolate somatic cells from the piglet's ears, use genetic engineering technology to complete the transformation, knock out 3 of the xenoantigen genes, and then transfer to 4 to 6 genes such as coagulation regulatory protein and hemotonic regulatory protein; Then, the modified cells were injected into the oocytes with the nucleus removed, and fused and recombined into reconstituted embryos. Finally, the reconstituted embryo was injected into the body of sows in estrus to simulate natural gestation. After 114 days, the piglets are born, grow, and until their weight and organ size meet the needs of animal experiments, which usually takes 2 to 4 months.
The breeding environment of these gene-edited pigs is very harsh, compared with the national treasure giant panda that is also a "hometown" in Sichuan. The piglets eat a nutritious and balanced high-protein food, and they can even be eaten directly; Drink purified water; Constant temperature and humidity in the living environment; Breathe purified air.
The stricter the implementation of the regulations, the more it can eliminate another major risk of xenotransplantation - cross-species infection, just like mad cow disease, AIDS, and plague, the bacteria, viruses, and parasites present in pigs may be transmitted to humans through transplantation. Bacteria, parasites and most viruses can be decontaminated by ultra-clean environment combined with caesarean section.
The R&D personnel of Zhongke Auge Biotechnology are holding gene-edited piglets.
Even so, the piglets currently bred can only be tested on animals. In the valley 150 meters northeast of the breeding center, the ultra-clean DPF (Designated Padogen Free) facility of Zhongke Auge, which began construction last year, will be put into use in May this year, creating an ultra-clean environment equivalent to a hospital operating room for piglets, which means that China's xenotransplantation is a big step forward in clinical trials applied to humans.
The first pig organ transplanted into the Chinese does not have to wait for a long time
For example, this week, Zhejiang Provincial People's Hospital completed the country's first minimally invasive artificial heart implantation operation; Two years ago, Austrian scientists used human stem cells to grow a sesame-sized heart organ ......At present, xenotransplantation is the most concerned in the world.
Dou Kefeng told Chao News reporters that more than ten years ago, the prospects for xenotransplantation in China were not clear.
At the end of 2010, Dou Kefeng, who was looking for gene-edited pigs abroad but could not, inquired that Pan Dengke of the Gene and Cell Engineering Office of the Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, had successfully knocked out the main xenoantigen genes of pigs in October 2010, making an important step forward in China's xenotransplantation.
We need gene-edited pigs, xenotransplantation experiments, can you breed such pigs? Dou Kefeng contacted Pan Dengke and asked the key question that was stuck in the neck.
I can. Pandenko agreed.
In this way, China's xenotransplantation has taken the first step towards the stage of animal experiments under helplessness, urgency, and coincidence.
Pan Dengke, who is now the deputy director of the Organ Transplantation Institute of Sichuan Provincial People's Hospital and the founder of Zhongke Aoge, recalled to the Chao News reporter that the cooperation from 0 to 1 has now expanded to double digits - the gene-edited pigs bred by Pandenke's team have participated in dozens of preclinical trials across the country.
After China's first gene-edited pig-monkey xenotransplant in 2013, NBC reported on it the next day, "indicating that our American counterparts are very concerned about our progress." Together with the team, Dou Kefeng and the American experts continue to improve the details of xenotransplantation through experiments and **.
The experimental monkey survived for 14 days, and the following year, a similar surgical approach was used in the United States, where the monkey transplanted with pig liver survived for 15 days.
In 2020, Dou Kefeng's team transplanted the heart, liver, and kidney of a pig into three monkeys, "which is to prepare for the more efficient use of pig organs after the large-scale promotion of xenotransplantation." This time, the monkeys who underwent an ectopic liver transplant survived for 26 days after surgery, setting a new survival record.
In October 2022, the world's first case of combined transplantation, "the monkey that received a combined kidney and liver transplant in the same period lived for 15 days; The monkeys that have had their ** and corneas transplanted at the same time, as well as the monkeys that have had cartilage transplanted, are all alive and in good condition, which gives us hope for clinical application. Dou Kefeng said that the monkeys that had their hearts transplanted survived for more than 20 days, which was less than expected, and the problem was in postoperative care and the use of immune preparations, which also brought valuable experience.
As an academician of the Chinese Academy of Sciences, Dou Kefeng submitted his own opinions and suggestions on different occasions and channels.
At present, there are more than 20 universities, hospitals, and institutions in China that carry out xenotransplantation experiments, and each has different priorities and breakthroughs.
Xenotransplantation research is like a long space journey, and the milestone of clinical application is like the arrival of humans on the moon. "When the conditions are ripe, xenotransplantation in China will not just stay in the laboratory, but take a step forward. Chen Zhonghua, an organ transplant expert at Tongji Hospital affiliated to Huazhong University of Science and Technology, said, "We are preparing for that day."
Comments:
1. It's only been a few days to survive now, and what humanity needs is how many years, five years, ten years, twenty years - sailor uf
2. Which organs can be transplanted - Bu Ze Hui W3
3. This can have [agree] support [agree] -- law search double gj
4. Liver transplantation without rejection will come out - Luo Xintian.
5. I hope to succeed as soon as possible - Jiaoyunying 099
6. Different species can be, so the same species does not need to consider the matching, it is not more dangerous. --Just 7o1
7. Chinese scientists and academicians are too experienced - Sang Erzhen ex
8. Hurry up and succeed,-- roll handsome AP
9. I've used animals before, but it's not successful, and now I don't know - Barbie murmuring in Linchao Lake.
10. Come on - smile and play.
11. When can I use it? --xpdiw