Donated organs from a pig
How realistic is this?
Organ transplantation has become one of the greatest achievements of medicine of the XX century, however, donor organs for transplantation are sorely lacking. In the European Union, waiting lists include about 50 thousand people, and every day 12 of them die without waiting for a suitable donor. According to the Russian Ministry of Health, a similar fate awaits about 60% of Russians who require organ transplantation. Since the creation of "organs from a test tube" is a matter of the distant future, the most realistic way out today is to use animal organs for transplantation.
Where do organs for transplantation come from? Sometimes from a living donor: in this way, a part of the liver, kidney or bone marrow can be transplanted to the recipient, for example. In other cases, so-called postmortem donation is used, after the donor is diagnosed with brain death or irreversible circulatory arrest. However, there are not enough donor organs, since many are not ready to consent to posthumous donation, and during transplantation it is also necessary to take into account the immune compatibility of the donor and recipient.
It is not surprising that back in the early 1960s, attempts were made to transplant human chimpanzee organs - one of these patients lived nine months after a kidney transplant. But even then it was clear that chimpanzees, who themselves are on the verge of extinction, will not be enough for everyone in need. Attempts to use baboons as donors, not to mention other mammals, have failed due to the rapidly developing rejection reaction.
However, in the late 1980s, new immunosuppressants appeared, which made it possible to more effectively restrain the development of the immune response to the transplant. Interest in xenotransplantation, the transplantation of animal organs to humans, has also revived. And by the mid-1990s, scientists agreed that pigs were the most suitable donor. Most of the tissues and organs of these animals are similar to human ones both in structure and function. True, ordinary domestic pigs and, accordingly, their organs are too large for humans. Therefore, miniature pigs were bred specifically for the purposes of transplantology.
In addition, pigs are easy to breed, so, for example, when making certain changes to the pig genome, it is possible to obtain genetically homogeneous animal lines by simple crossing, which can give universal organs for transplantation.
The main obstacle to "pig" donation is the strong rejection of pig xenografts by the human immune system. However, advances in genome editing, primarily CRISPR/Cas editing systems, allow us to overcome tissue incompatibility. With their help, the immune characteristics of animals can be brought closer to human ones. So, pigs have already been created whose genome lacks certain proteins-antigens that cause immune reactions in the human body, or, conversely, some useful human proteins are produced.
All this has made it possible to improve the survival rate of pig transplants – so far, however, only in experiments on primates. For example, pancreatic islets of Langerhans producing the hormone insulin were transplanted relatively successfully. But in the end, these transplants were rejected, despite strong immunosuppression. When transplanting a pig kidney, several animals "lasted" more than a year. It is possible that in the near future such xenotransplantation will be done to severe patients who have little chance of receiving a kidney from a human donor.
There is another approach to the problem of rejection of animal organs – to reduce the reaction of the human immune system to foreign antigens, so that the latter are perceived as "their own". There are two ways to achieve this. For example, to partially kill the human bone marrow of a donor, and infuse there hematopoietic stem cells of a pig. Subsequently, the descendants of donor cells populate the thymus, where the maturation and immunological "training" of T-lymphocytes takes place, as a result of which immune cells capable of attacking the body's own proteins (and in this case, the pig's body) die. It is also possible to transplant only pork thymus, freed from mature T-lymphocytes – the process will be similar.
According to scientists, the combination of genetically engineered modifications of donor animals with increased tolerance of the human immune system will make it possible to achieve real success in xenotransplantation. True, there is also a safer alternative – bioengineered organs, when creating which the patient's stem cells are populated either by the connective tissue framework of a real organ, freed from cellular elements, or a framework obtained using three-dimensional printing, but such transplantology is only taking the first steps so far.
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