How old is the rabbit in 2022, which belongs to the rabbit age comparison table.

How old is the rabbit in 2022? Recently, many foreign media reported that Langone Medical Center of new york University had just conducted a special experiment-a medical team in the United States successfully transplanted a genetically edited pig into a brain-dead female patient with renal insufficiency, and the patient's serum creatinine returned to normal. At present, this new kidney has good filtration and production functions.

If the operation is successful, it will show that pigs can be safely used to save lives. This makes people curious: what is the significance of this operation? Why are pigs so powerful? When can it be used in clinic and for patients?

New bottled "old wine"

At present, the reason for doing this operation is that it has certain innovative significance-it is verified that the heterogenous animals that knock out α-gal will not cause hyperacute rejection of human body, and the development of heterogenous technology goes further.

Photo: eGenesis.com.

Generally speaking, it may cause rejection, and some rejection reactions occur very quickly and violently, often necrosis within a few hours, and the disease soon dies. This is hyperacute rejection, which is common in xenotransplantation, the same blood type and pre-stored antibodies.

However, in the field of professional medical care, this operation is not enough to solve all the problems of different species, and there are some elements of pleasing and showing.

Specifically, first of all, the recipient is a brain-dead woman. With the consent of her family, the doctor transplanted the pig into the vein of the recipient's thigh instead of the internal iliac artery and vein as usual. This is only for the convenience of observing the appearance and functional state of the kidney from the outside, not to prolong the life of patients with renal failure.

When asked how long the kidney survived in the patient, the surgeon just kept silent: "The effect exceeded our expectation", "the amount you expected", "creatinine returned to normal" and "pig kidney took effect almost immediately".

According to foreign media reports, the experiment ended after 54 hours of continuous observation-and the life support facilities of the brain-dead women were also removed, and the experiment ended. If we continue the experiment, the acute rejection of human body may destroy the pig kidney, the experiment will fail, and the so-called "xenotransplantation era is coming" argument will be falsified.

An alien with a long history

Why can aliens be widely used? At the beginning of life, people's physical function is in good condition, just like a new car they just bought; However, with the growth of age, new cars become old cars and may need to be "patched".

But to repair parts of the human body, we need real. It may be artificial (such as artificial joints and artificial hearts), autologous (such as skin) or allogeneic, so there is surgery.

Human exploration has to start from hundreds of years ago. /kloc-in the 0 th and 7 th centuries, someone tried to transfuse animal blood to a large number of human beings who lost blood, and the patient died on the spot; At the beginning of the last century, doctors also increased their exploration of xenotransplantation, transplanting rabbits into children with renal hypoplasia; Later, other doctors began to look for humans from goats, pigs and primates, but because the human body has a strong immune response to different species, it is enough to kill them.

Humans finally realized that heterogeneous species can cause very serious rejection; From then on, people began to focus on human experiments, and completed the first successful kidney transplantation on 1954. Because the donor and the recipient are identical twin brothers, there is no rejection at all.

However, not every patient is so lucky, and the subsequent human body still relies more on foreign bodies, and solving rejection is the key.

It is reported that the main solution at present is to carry out ABO blood group, HLA matching and lymphocyte cross-matching tests before operation to select those donors and recipients with the least rejection for transplantation. However, the patients need to be immunized (such as cyclosporine and azathioprine). ) for life, thus rejecting the outside world with your own immune system. The price is that infectious immunity will be reduced and it is easy to get sick.

Nowadays, such a set of "matching-lifelong medication" allogeneic transplantation has become a clinical routine.

But now there are far more patients to be accepted every year than those who can be used for transplantation. According to statistics, there are about 300,000 people in China every year. Due to economic and social constraints, only about 65,438+/kloc-0,000 people can receive transplantation every year. There are about 6.5438+0.2 million patients waiting in the United States every year, and less than 30,000 people can successfully transplant. This also gave birth to the black industry of "buying and selling" to a certain extent.

How to solve the problem of donor shortage has become a concern of academia and industry, and everyone has returned to a heterogeneous perspective.

Why pigs become "better" donors?

It is reported that after a round of failed experiments on goats, baboons, rabbits and dogs, pigs have been accepted by people and regarded as ideal donors, because pigs are abundant, and many of their sizes, such as hearts and kidneys, are similar to those of people, and their functions are similar.

Comparison of Body Shape between nai500.com People and Pigs

However, even the transplanted pigs will still face two problems: first, immune rejection, if the transplanted pigs are not immune homologous, it will easily lead to our own immune cells and eventually lead to failure; Secondly, transplantation may exist, causing immeasurable harm to the recipients.

In order to solve the above problems, scientists try to use gene editing technology to "sweep away" many biological barriers between pigs and people and promote heterogeneity.

It is reported that the United States took the lead in cultivating medical pigs. In 2003, Revivicor created an α-gal knockout transgenic pig (GTKO pig) in the world. So far, xenotransplantation in the United States has passed clinical trials, and GTKO pig has become an internationally recognized donor base. The pig used in this news report is Revivicor Company.

Photo: IC photo

However, this is only the foundation of heterogeneity, and there are still many problems to be solved. At present, α-gal knockout can escape hyperacute rejection, but it is only one of the targets of hyperacute rejection, and there are many other targets, such as CMAH gene, β4GalNT2 gene, ASGR 1 gene and so on. If all of them are knocked out, the possibility of hyperacute rejection of xenotransplantation may be reduced to a lower level.

CMAH gene: N- hydroxyacetylneuraminic acid (Neu5Gc) produced by the enzyme encoded by this gene is an important non-galactose antigen of xenotransplantation rejection. The existence and expression of CMAH gene can cause xenotransplantation immune rejection;

β4GalNT2 gene: The enzyme encoded by β4GalNT2 gene can transform Sd(a) blood group antigen. When pigs arrive in primates, blood group antigen Sd(a) can bind with immunoglobulin, causing immune rejection.

ASGR 1 gene: ASGR 1 protein is expressed in porcine vascular endothelial cells, which can be recognized and attacked by immune cells of the recipient, causing acute intravascular coagulation and rapid inactivation in pigs. At the same time, it can also induce thrombocytopenia in recipients after xenotransplantation.

In addition, pigs can also introduce some human genes, such as CD55 and CD59, which are important human complement inhibitors and can reduce the occurrence of hyperacute rejection and inflammatory reaction, and can be understood as natural immunosuppressive regulators.

However, besides hyperacute rejection, pigs may also face acute rejection based on ABO blood group and HLA complex, which may cause serious endothelial thickening, injury, ischemia and thrombosis after transplantation. In order to avoid these reactions, more genes will be eliminated accordingly. In addition, there are cell rejection and chronic rejection; The mismatch of some physiological functions between different species is still unclear; Moreover, all kinds of known or unknown pathogens carried by pigs are only partially solved at present.

Judging from this operation, it is reported that the donor gene editing pigs only knocked out the α-gal gene, which is only a step in the long March, and it is far from completely avoiding all kinds of rejection in the human body.

In addition to these, there are complex problems: even if human beings accept heterogeneous research, if they are used in clinic, xenografts may carry infectious agents to xenotransplantation recipients and spread widely, which is unpredictable.

Innovative forces compete for the blue ocean market

As mentioned above, combined with the operation cost of 300,000-400,000 yuan per patient, this is a huge and unsatisfied market. Heterogeneity has a broad stage, and some enterprises have entered this blue ocean field.

For example, in September 2022, Hangzhou Qixin Biotechnology Co., Ltd., founded by Professor George Mcdonaldchurch and Dr. Yang Luhan, pioneers in the field of gene editing, announced that it had made a new generation of heterogeneous prototype-"Pig 3.0", which had better immune compatibility and eliminated porcine endogenous reverse transcription (PERV).

Zhongke Og was founded by Dr. Pan, a leading pig experimental figure in China. Through gene editing and technology, more than ten kinds of transgenic humanized pigs were cultivated for xenotransplantation research and development, which solved the shortage of clinical transplantation. After its recent completion, it is preparing to establish a medical-grade heterogeneous transplantation medicine donor in the ultra-clean pig facility (DPF) to prepare for clinical trials.

As for the overseas market, eGenesis, the sister company of Qixin Bio, completed the $65.438+0.25 billion Series C in the first quarter of this year. At present, it is building a "three" model and testing the effectiveness and safety of genetic engineering. Clinical trials are expected to begin in 2022.

In addition to the GTKO pig for skin xenotransplantation, the genetically edited pig "GalSafe pig" developed by Revivicor was approved by the US Food and Drug Administration (FDA) at the end of last year and can be used for eating and producing products.

In addition, Miromatrix Medical, which specializes in human xenotransplantation of pigs, was listed on NASDAQ in June this year, becoming the first heterogeneous company to be listed. It is expected that by the end of 2022, its bioengineering will begin human clinical trials supported by external auxiliary systems.

Predictably, this news will more or less lead to the soaring share price of Miromatrix Medical and the rising valuation of many companies in the secondary market. But objectively speaking, considering the current research and development and industry status, the new era of heterogeneous animals replacing human bodies is far from coming, and scientists need to continue to explore.

Extended reading

Cognitive materials | Replace the body with a "part" and "continue" artificially.

refer to

Give pigs to humans, how long do we have to go? A piece of ginger;

Heterologous transplantation milestone! People have successfully transplanted pigs' kidneys. Why pigs are ideal? Cop China;

The world's first pig kidney transplant: it can't bring a new era, but it can only bring about a surge in related stocks, Dr. Philip.

The above is related to the size of rabbits in 2022, and it is about sharing. Read the rabbit age comparison table, I hope this will help everyone!