A unique clinical trial is underway right now at the Massachusetts General Hospital (USA). Doctors transplanted genetically modified pigs into six patients with severe burns. The first operations were carried out back in October, and the final results of the experiment will be reported in July. At the same time, volunteers are being trained in China for transplanting internal organs of GM piglets. In the meantime, the genetic compatibility of pig cells with human cells is tested in laboratory conditions. RIA Novosti is investigating whether interspecies transplantations are successful and how scientists have ensured that the skin of animals is not rejected by the human body.
Survive with someone else's heart
The first successful interspecies transplantation took place back in 2013. Then American researchers transplanted genetically modified pigs' hearts into the abdominal cavity of five Anubis baboons, leaving their own. The donor animals lacked the 1,3-galactosyltransferase enzyme gene located on the inner lining of the vessels of all mammals, except primates. The production of antigens to this substance could lead to the formation of blood clots in monkeys that received new organs.
Also, in the cells of donor pigs, human versions of two proteins, thrombomodulin (CD141) and CD46, were produced. The first prevents blood from clotting after surgery, the second blocks the immune response and thus protects foreign tissues from destruction.
As a result, one of the baboons participating in the experiment lived with a foreign organ for almost three years.
Four years later, researchers complicated the task: 14 baboons' hearts were replaced by pork hearts. The first ten monkeys operated on died within 40 days of the procedure - mostly from liver or heart failure.
Then the researchers began to transplant organs to monkeys, which were connected to a special apparatus before transplantation. He pumped an oxygenated mixture of blood and nutrients through them. Also, all monkeys operated on were given special medications to slow down the growth of pig hearts. Otherwise, they grew very large and damaged adjacent organs.
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As a result, two baboons lived after transplantation for three months, and another two for six months. The reason for the death of animals is the size of the transplanted hearts. They have almost doubled since the operation, and tissue necrosis began in the monkeys.
Human parts
In 2019, Chinese scientists reported that they had developed a breed of pigs whose organs could be safely transplanted to humans. In their DNA, the gene for 1,3-galactosyltransferase and the specific endogenous porcine virus (PERV), a region embedded in the genomes of almost all known breeds of these animals, are disabled.
Experiments have shown that when pork and human cells are co-cultured, the latter are infected with this virus. As a result, PERV produces RNA in them and the number of its copies in the genome increases. Such infected cells may well transmit the virus to healthy cells. This means that with transplantation of large porcine organs - for example, heart or liver - infection is not excluded. And how the human body will react to it is unknown.
GM piglets genetically compatible with humans. It is believed that their organs can be transplanted to humans.
In addition, eight human genes are actively working in the DNA of artificially bred animals, and those parts of the genome that could cause immune rejection during transplantation of pig organs to humans are turned off. At the same time, scientists do not exclude that the immune system of patients can nevertheless react to foreign organs by recognizing rare proteins in their cells. But this can be dealt with with immunosuppressants.
According to the researchers, the company will conduct preclinical trials in the summer, and in the next five years will begin testing the transplants of pig organs in humans.
New skin
The first person to receive an animal organ transplant was an American with extensive body burns. His name has not yet been announced. In October 2019, at the Massachusetts General Hospital, he received the skin of a genetically modified pig, measuring five by five centimeters. With this patch, under the supervision of doctors, he spent five days, during which the researchers did not record any complications. Then the skin was removed and the anti-burn treatment was continued.
The transplant was performed as part of a clinical trial, which is being conducted by XenoTherapeutics for the second year. According to the FDA (the American equivalent of the Ministry of Health), the final results of this testing will be known by mid-July.
The experiment uses the skin of pigs in which the 1,3-galactosyltransferase gene is disabled. Therefore, human immunity is more tolerant to their cells and there is no instant rejection of the animal organ.
In addition to swine, the patient also received a skin graft from a dead person. After five days, the scientists removed both patches and did not notice any difference between the state of the wound underneath. This suggests that the immune system took the animal's organ for a human. The patient then received skin grafts from his own thigh and the wound healed successfully.
The researchers hope that in the near future, for severe and extensive burns, pigskin can be used as a temporary patch.
Alfiya Enikeeva