A pig can be disassembled not only for fat and meat, but also for … prostheses for heart patients, liver recipients and those who are at risk of gangrene, porcine prostheses of deficient vessels - skeletal skeletons of small arteries - are being tested at the Kharkiv Institute of Cryobiology and are already preparing to move to Israel
Usually a person has enough of his own blood vessels: if they are not clogged with cholesterol plaques, clogged and not torn, then a person does not have to think about a lack of blood vessels. However, every year Russians need tens of thousands of new vessels - artificial, donor or their own, transplanted from one site to another.
Synthetic or natural vessels are necessary for coronary artery bypass grafting in ischemic heart disease, insertions in radical operations and liver transplants, for the surgical treatment of injuries and vascular lesions threatening gangrene, for example. There are more than enough indications for vascular prosthetics, the main thing is that all are associated with a high risk of death.
PROBLEMIC VESSELS
If we are talking about capillaries - small peripheral vessels, then they do not need to be transplanted, such vessels can be grown inside the patient himself. To do this, it is enough to inject a circular DNA molecule into the affected area, which contains the human VEGF gene (Vascular Endothelial Growth Factor). The protein synthesized from it also stimulates the growth of capillaries. Since the capillaries consist of a minimal set of cells, there are no problems with vascular inferiority, says Roman Deev, Ph. D., Managing Editor of the Cell Transplantology and Tissue Engineering journal.
Arteries and veins do not have fundamental differences in structure, but the former carry blood from the heart, the latter - to the heart. The vessels of the microcirculatory system (capillaries, venules, arterioles, etc.) are the "bridge" between the veins and arteries. The structure of arteries and veins is the most difficult. They consist of a dozen types of cells, each of which is represented by several layers. Depending on the structure of the arteries and veins, they are divided into types: elastic, intermediate, muscle. The types of vessels differ in thickness, tissue composition, number of cell layers, mechanical characteristics and functions. In the hierarchy of complexity, capillaries are at the last step. They are formed by just one layer of flattened cells - endothelial cells.
“Grow small vessels? Yes, no problem, - continues Roman Deev. “Moreover, there is evidence that smooth muscle elements and fibroblasts are involved in the process of vascular formation triggered by the VEGF genome. So, over time, capillaries can evolve into larger vessels. This is indirectly evidenced by the data of clinical trials”. If a vessel larger than a capillary needs to be restored not in the future, but "here and now," then the task becomes much more complicated. And here one cannot do without surgical prosthetics.
In vascular surgery, doctors use the native (autologous) vessels of patients and synthetic prostheses. So, you can replace a section of a large vessel, such as the aorta, with synthetics. According to the president of the Russian Society of Angiologists and Vascular Surgeons Anatoly Pokrovsky, synthetic prostheses last a long time (up to 30-40 years), and withstand high blood pressure, and are combined with the regenerative processes of the surrounding living tissues. The most vulnerable and problematic vessels are small diameter arteries (less than 6 mm). It is because of them that coronary heart disease and gangrene develop.
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Medicines that improve blood circulation are effective for only a few months. And synthetic prostheses, suitable for large vessels, are not at all suitable for small-diameter arteries: the suture site (anastomosis) becomes overgrown with connective tissue, the vessels become clogged, and thrombosis begins. Autologous vessels, that is, obtained from the patient himself, are recognized as the "gold standard" of small-diameter vascular prostheses. No biotechnological miracles: surgeons simply cut out the saphenous veins and replace them with coronary arteries in the heart, for example. This is how not only coronary artery bypass grafting is performed: according to the same principle, surgeons supply vessels to other organs and body parts.
VESSEL FERTILIZER
The VEGF gene is already being used in research and for the treatment of limb ischemia. Thus, the Federal State Institution “Russian Cardiological Research and Production Complex of the Ministry of Health and Social Development of the Russian Federation” received permission for clinical trials of a drug containing the gene. Another prototype based on the VEGF165 gene was developed at the A. N. Bakulev Scientific Center for Cardiovascular Surgery and the Institute of Gene Biology of the Russian Academy of Sciences. And the product of the Institute of Human Stem Cells has already passed clinical trials and received a registration certificate from the Ministry of Health.
About 15 thousand coronary artery bypass grafting operations are performed in Russia annually. And there are several times more needy people. According to Russian and foreign doctors, in about a third of patients, their own vessels cannot be used for prosthetics. Some people need too many vessels, so their own is not enough; in others, degenerative changes are too significant, therefore, doctors do not dare to change the awl for soap.
“There are also patients from whom the vessels cannot be removed due to anatomical features,” explains Boris Sandomirsky, Doctor of Medicine, Head of the Department of Experimental Cryomedicine at the Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine.… - Another problem is the limited "shelf life" of autologous grafts: they have been working in the new place for about five years. So it turns out that, for example, for repeated coronary artery bypass grafting, the vessels may not be enough.
DEFICIENT VESSELS FROM PIG
Scientists from the Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, under the leadership of Boris Sandomirsky, are trying to implant pig vessels in humans. The idea is to create pork vessel frames that can be populated with vascular cells, thus obtaining full-fledged prostheses. Almost like Paolo Macchiarini, who creates tracheal scaffolds and populates them with stem cells. But in the Sandomierz bioreactor, the cells are not stem cells, but vascular. “These are two- or three-layer tissue-cell structures grown in vitro on the basis of a vascular framework,” explains Boris Sandomirsky. “At the first stage, smooth muscle cells of the arterial walls are layered on it, then - the endothelial cells of the recipient”.
Sandomirsky is sure: natural cell-free xenogenic (derived from animals) frameworks are much better than synthetic materials; they have excellent mechanical properties and in the recipient's body are gradually transformed by the extracellular matrix of the recipient itself. Boris Sandomirsky has already received porcine vessels, of which only connective tissue frameworks remained (there was no muscle layer or endothelium in these "tubes").
VASCULAR BIOTECHNOLOGY
Biotechnologists have been trying for several years to create analogs of small and medium-sized vessels using donor tissues or the patient himself, cell technologies and 30-printers. For example, biologists sewed glass tubes to animals, after removal of which frameworks of connective tissue remained under the skin. They were suitable for the reconstruction of the vascular bed, but still they did not justify themselves. “A couple of years back, for example, biologists have created a cliché in the form of endothelized tubes made of polylactic acids,” Roman Deev tells “World Details”. When the biodegradable scaffold dissolved, the culture of vascular cells seeded on it remained - a small diameter blood vessel was obtained. In 2011, researchers from Germany under the leadership of G nterTovar,project manager from the Fraunhofer Institute for Interfacial Engineering and Biotechnology, suggested printing vessels on a three-dimensional inkjet printer with polymer ink. The ink tanks are still being tested. Scientists from Novosibirsk and Germany (Research Institute of Cardiology, Siberian Branch of the Russian Academy of Medical Sciences, Siberian State Medical University of Roszdrav and the University of Rostock) populate the scaffold obtained from the vessels with stem cells. That is, they work exactly like Macchiarini, only at the base is not the trachea, but a blood vessel - a smaller and thinner hollow structure. Biotechnologists also have a slightly different approach - to populate the collagen matrix with stem cells, rather than a "decellular" vessel.proposed to print vessels on a three-dimensional inkjet printer with polymer ink. The ink tanks are still being tested. Scientists from Novosibirsk and Germany (Research Institute of Cardiology, Siberian Branch of the Russian Academy of Medical Sciences, Siberian State Medical University of Roszdrav and the University of Rostock) populate the scaffold obtained from the vessels with stem cells. That is, they work exactly like Macchiarini, only at the base is not the trachea, but a blood vessel - a smaller and thinner hollow structure. Biotechnologists also have a slightly different approach - to populate the collagen matrix with stem cells, rather than a "decellular" vessel.proposed to print vessels on a three-dimensional inkjet printer with polymer ink. The ink tanks are still being tested. Scientists from Novosibirsk and Germany (Research Institute of Cardiology, Siberian Branch of the Russian Academy of Medical Sciences, Siberian State Medical University of Roszdrav and the University of Rostock) populate the scaffold obtained from vessels with stem cells. That is, they work exactly like Macchiarini, only at the base is not the trachea, but a blood vessel - a smaller and thinner hollow structure. Biotechnologists also have a slightly different approach - to populate the collagen matrix with stem cells, rather than a "decellular" vessel. That is, they work exactly like Macchiarini, only at the base is not the trachea, but a blood vessel - a smaller and thinner hollow structure. Biotechnologists also have a slightly different approach - to populate the collagen matrix with stem cells, rather than a "decellular" vessel. That is, they work exactly like Macchiarini, only at the base is not the trachea, but a blood vessel - a smaller and thinner hollow structure. Biotechnologists also have a slightly different approach - to populate the collagen matrix with stem cells, rather than a "decellular" vessel.
The tests are in full swing. “We planned to test the biocompatibility of the resulting scaffolds. It was also necessary to find out whether an immune rejection reaction develops, whether blood clots are formed, says Professor Sandomirsky. “It turned out that even bioreactors are not needed for vascular prostheses: the organism of experimental animals itself builds up the necessary cell layers.” During the year, scientists transplanted such prostheses, first a dozen mice, then 15 wild rabbits. Not without losses, biologists admit: some animals died. “You must understand that our experiments are going on in the most severe conditions,” continues Boris Sandomirsky. "We do not use any anticoagulants or immunosuppressants."
This means that if the vessels have taken root, then this is forever: blood clots are not formed, the transplants are not rejected by the immune system. A good result is evident: one of the rabbits became pregnant and gave birth a month after the operation. No pathologies were observed during pregnancy and childbirth, the rabbits were born healthy. And this is after the replacement of the abdominal aorta! What do we need rabbits and mice, the reader will ask a question? When will all this research become easier for a person? Boris Sandomirsky says that very soon: “We have an agreement with our colleagues from Israel. They are ready to conduct certification and clinical trials. This process will take one and a half to two years."
RECIPE FOR PREPARING FRAMES
Under aseptic conditions for 30 minutes. after slaughter, remove the vessels from the pig. Rinse three times with saline cooled to 4 ° C with added antibiotics (100 IU / ml penicillin, 100 mg / ml streptomycin, 6 mg / ml fluconazole). Place the arteries in sterile cryostable containers and place them in liquid nitrogen vapor. In this state, the vessels can be stored indefinitely. If necessary, take it out of the cryocontainer and warm it up in a water bath at 37 ° C. Within 90 min. irradiate after warming up. The scaffolds can be transplanted into an animal (human) organism without first being placed in a bioreactor: if there were a scaffold, the cells would grow on their own.
The professor has almost no doubts that pork vessels will be suitable for humans. After all, pig heart valves are transplanted to people (including in Moscow). And after clinical trials or in parallel with them, Boris Sandomirsky plans to create a bank of pig vessels: "This project will be commercially profitable: one vascular prosthesis will cost about 10-30 thousand euros." The need for vessels is estimated at tens of thousands annually. Without them, people die or become disabled. So transplantologists have someone to work for.