are you rosy and you grunt and squeal like pigs. And yet, the bristle cattle is a mixture of “German Landrace” and “Great White”, in a comfortable barn to the North of Munich is something special. For years, Eckhard Wolf, head of the moor versuchsguts of the Institute for animal tries breeding and biotechnology at the Munich Ludwig-Maximilians-Universität, pigs genetically change so that you have your organs transplanted and the immune system of the human can be tolerated. Now, Tests indicate that such Pinbahis a pig’s heart to survive no longer than three months, and even up to 195 days in the body of baboons and their service do. “A milestone on the way to clinical application,” says Wolf.
Acute defensive reaction outwitted
More than 400 patients with acute heart failure would be needed in Germany by 2017 a heart transplant. Only 269 of the life-saving operations were organs – mostly due to lack of donors. Because pig hearts are similar to human, hope researchers and Physicians have long pointed out that after decades of research, finally “Xenotransplant” – the Transplant of animal organs to keep patients, at least as long as the life, to human.
But, unfortunately, the human body’s immune system does not react with the instant destruction of human bodies, the “Hyper acute rejection”. On the surface of pig cells, molecules that are recognized by the immune cells of the people as a foreign seats. These must be removed before Xenotransplantation can be conceived. The pigs are bred on the moor the experimental farm, so genetic changes, which, if you will – pork – friendly for the people, so that the foreign tissue in the patient only survived, but also its function: the pumps can meet in the case of a heart transplant.
Less pork, more human
One of the most important changes relates to the Gene for an enzyme that paints, in a sense, the pigs, the typical marks on the surface of the cells, the “alpha1,3-galaktosyl transferase”. Organs of pigs, to whom this Gene is missing, you will not be attacked after a Xenotransplantation by the immune system so aggressively.
But this alone is not enough. Two more genetic changes it needed to make in the moor of the pigs the experimental farm to grow their hearts in baboons is not only a maximum of 57 days, special up to 195 days worked, as the researchers report in the journal “Nature”. So the researchers introduced a human Gene (hCD46) into the pig genome, whereby the surface of the pig cells appear the immune cells of the patient a piece of “human”. In addition, the blood coagulation has to be adjusted in the pig heart conditions in humans, including alterations in the Thrombomodulin Gene is necessary.
Special nutrient solution keeps the heart fresh
However, there are not only genetic tweaks that have brought the Xenotransplantation now in the vicinity of the clinical applicability. By the German research Foundation, with a 13 million Euro funded joint “biology of xenogeneic cell, tissue and organ transplantation”, in which basic researchers and Physicians work closely together, also found out that the pig organs should not be preserved during the transplant better, as usual, in an ice-cold solution. One to eight degrees Celsius temperature, nutrient, oxygen and hormone-enriched blood-based liquid aspect of the organs better.
Nevertheless, the experimental animals were killed at the beginning, after about 40 days. The pig’s heart, which originated due to the difference in Size between baboon and pig out of a young, six-week piglets grew more. This Problem, the research team triggered the cardiac surgeon Bruno Reichart, the head of the compound, together with Eckhard Wolf, by slowed heart growth medication. “The Problem is when people are not relevant, because the heart would not be used by adult pigs, which then grow even more,” says Wolf. However, in order to keep the organs in the experimental animals at least three months of the life of, and to prove so, by Definition, the feasibility of the xenograft ion, were the treatments necessary. So four of the five monkeys lived at least three months, two even six months. Only one died already after 51 days.
the First Tests on humans is not planned
If and when the first Tests of the pig hearts to patients is feasible, as Eckhard Wolf is not really set. “It is technically possible, it would be now.” However, since a company in the USA in the 1990s had claimed, already in the year 2000, many people would be running around with pig heart, hold you with forecasts. “The only cause disappointment, and this step, a pig heart to a human, should be very carefully prepared.” An error, and the work of many decades would be undone.
the guidelines of the International society for heart-lung transplants, first clinical Trials would be justified to the people anyway, only then, if in experiments on baboons 60 percent of the animals survive for three months and the test series, “includes a minimum of 10 animals surviving for this period of time and there are indications that longer Survival is possible,” writes the heart specialist Christoph Knosalla from the German heart centre of Berlin, in an accompanying commentary in “Nature”. On the other, the Wolf, the experimental farm, the pigs in the Bog while already exceptionally high standards of hygiene are kept, so that they are free of CMV virus, the patient could possibly be dangerous. For a clinical application, the animals have to be reared in special containers, before organs can be removed.
retroviruses in the pig genome
Not all the hurdles have to be overcome by Hygiene. So far, stuck in the genetic material from pigs, the genes of retroviruses, so-called Pervs. Although there are no reports that this virus had triggered side-effects in patients, which in individual pig tissue transplanted cases was audited. However, admission authorities may request, to release the pig genetic make-up of these Gene segments. That is, in principle, possible, has shown the group of researchers led by George Church at Harvard University in Cambridge, Massachusetts, some time ago, with the help of the Gene-scissors Crispr/Cas9 to pig cells.
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Knosalla, in his comment, the question of whether the xenograft ions are due to the rapid development of mechanical, artificial pumps. “So far, Xenotransplantation was such an Alternative, because the organs have not thought about long enough,” admits Wolf. The have now changed. “Because the side effects of such pumps can be quite dramatic: bleeding, infection, heart failure, brain infarctions, and some of the devices that make a noise like a concrete mixing machine.” Organs from animals are adapted to the requirements of the continuous Transport of blood, however. “This suggests that we should explore the possibilities of Xenotransplantation.”
