They lay pigs: how experimental Siberian mini-pigs help medicine

About 120 mini-pigs live on the farm of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences (ICiG) in  Novosibirsk , bred specifically for experimental scientific and medical tasks, including for practicing operations and procedures that are planned to be carried out on humans in the future, as well as safety checks and the effectiveness of the products that a person is planned to be implanted.

Efforts to create suitable research pigs began as early as the 1960s, but success was not achieved until the early 1990s.

“In 1991, we conducted the first crossing between large white sows from the Bolshevik breeding farm and miniature boars, which were brought from Svetlogorsk. From them, our breeding group went – mini-pigs of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, – Sergey Nikitin , Ph.D. – Each area has its own climatic conditions, its own characteristics in terms of feed, microflora. We have managed to breed pigs that are well adapted to local conditions. Animals from vivariums, for example, are not adapted to life in their natural environment. We also needed a group that is technologically advanced and easy to maintain.”

Mini pigs are “mini” only when compared to regular pigs, which can weigh up to 500 kg. For experiments, individuals are required, in terms of mass and size of organs close to humans – from 40 to 100 kg. Also, “experimental” pigs should not have a thick fat layer, so greasy breeds are not suitable for medical tasks.

“Different operations require different pigs. People are also different in age, height, and weight, so we try to have the whole scale – small, medium, and large. In addition, only meat-type pigs are suitable for medical tasks. They shouldn’t be greasy. Can you imagine how to break through such a layer of fat? It’s easier to do liposuction,” says Nikitin.

In the last year, despite the difficulties that science has faced against the backdrop of sanctions, the demand for mini-pigs has remained still high.

Most often, the farm supplies pigs to the NMIC them. ak. E.N. Meshalkin, where new approaches to the surgical treatment of cardiovascular pathologies are being developed, and to the Angioline Research company, which creates coronary stents, heart valves and other medical products for cardiac operations.

“We use mini-pigs from the farm of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences as a model for operations – the implantation of new products developed by us.

Pediatric cardiac surgeons are especially fond of mini-pigs, because mini-pigs are small in weight, their heart sizes are approximately the same as in children of preschool and primary school age, ”said the director of the Institute of Experimental Biology and Medicine of the National Medical Research Center. ak. E.N. Meshalkina, Doctor of Medical Sciences Irina Zhuravleva .

For similar tasks, they are also used in Angioline Research.

“According to the law of the Russian Federation , high-risk devices – in our case, these are implantable medical devices – must be tested on animals before registration. Our main products are coronary stents and we are required to test them on at least six gilts before we bring them to market to make sure the products are safe and effective. We implant a stent in a pig, after a certain time we remove it and check whether the animal’s body and the stent itself have undergone any changes,” Dmitry Trebushat, head of the development department at Angioline Research, told Gazeta.Ru. “We take mini-pigs specifically for the experiment, put them on the operating table, observing ethical standards and the European Convention on the Protection of Animal Rights, perform the operation, after which we humanely remove them from the experiment.”

Although mini-pigs are close to human in size, they are not used to create tissue implants of valves or blood vessels – this is not economically feasible.

“To create implants, we use what would otherwise go into sausage. The pig for slaughter weighs 150 kg, we buy a small part of the pericardial bag weighing 50 g from this pig, with certain quality obligations, and then use it in our products.

Mini pigs are an exclusive product, pigs that were originally bred for experimental purposes.

In the same ICG, there are not so many of them. And if we are talking about production based on the materials of the same xenopericardium (material of the heart bag), large volumes are required there, ”explains Trebuchat.

Pig heart valve is better than artificial

The development of heart biovalves began in the 1950s, and they became widespread after the 1970s. To create them, animal tissues are chemically processed into “biological plastic” and heart valves are formed from them, which are then implanted in humans. Such valves are developed and then tested on mini-pigs and at the N.N. ak. E.N. Meshalkin.

Today, biological heart valves are widespread throughout the world due to a number of advantages over artificial materials.

“For example, porcine or bovine xenopericardium, which is used worldwide mainly for the formation of the cusp apparatus of a prosthetic heart valve, is biomechanically superior to existing synthetic analogues,” says Trebuchat. – Its elasticity allows the same work, to maintain the flow of blood, as well as a person’s own heart valve. There are mechanical heart valves, but even they have their own problems – first of all, thrombosis.

And the biological valve, in terms of biomechanical properties, is more similar to the native (original human) heart valve – it closes and opens about 60 times per minute, and the blood flows freely without unnecessary thrombosis.

Is it worth it to grow donor organs in pigs?

Pigs have been considered as a potential source of donor organs for humans for several decades. To do this, pigs must be genetically modified – their tissues are incompatible with human ones. So far, however, it has only gone as far as a few experimental operations. In one of them, the kidneys and thymus gland of a pig were transplanted into a patient whose brain had already died. In another patient, he received a porcine heart, but died two months later of heart failure, which could be caused by porcine cytomegalovirus or taking drugs with antibodies to porcine cells.

Such experiments are interesting from the point of view of the development of science, but such an approach is unlikely to lead to providing society with a sufficient number of donor organs, Zhuravleva believes.

“This is not a promising direction. More promising in this regard are tissue engineering, 3D bioprinting, and so on. It is possible to transplant a heart or other organ from a genetically modified pig, but it is very expensive. It is necessary to carry out the necessary genetic modifications to the pig, feed it, raise it … Imagine what these costs are. And the good result of all this work is extremely doubtful.

3D bioprinting, on the other hand, is printing from the patient’s own cells, that is, no rejection reactions – these are their own cells. They can be grown in a flask, in a test tube, in a reactor and implanted in a specific patient,” she explained.

With the help of 3D bioprinting, it is possible to form an entire organ. So far, in world practice, experience is limited to simple structures, but the cultivation of complex volumetric organs is not far off.

“Nowhere else are complex organs grown completely, only very small ones, for example, the trachea. No one has yet grown a heart or something like that, but I think this is a matter of literally the next decade. This year we should also have a 3D bioprinter, and we will be engaged in similar experiments. The heart, of course, cannot be printed immediately. Let’s try to get a fragment of myocardial tissue for now, ”said Zhuravleva.