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Dozens of Russian clinics want to use cellular products created at the Institute of Cytology of the Russian Academy of Sciences. It seems in vainDmitry Fialkovsky, "Expert North-West", 12/22/2008
The operating room of the I.I. Janelidze Research Institute of Emergency Medicine. On the operating table is a patient with a fourth–degree burn of the skin of the face and right hand. The surgeon removes 1.5 mm of the upper layer of skin from the patient's back with a special machine. The "flap" is passed through another machine, which makes special slots in it – this allows you to increase the area of the skin layer by one and a half times. The resulting "mesh" is superimposed on a huge gaping wound on the arm. The wound is closed for a while.
But with supercritical burns, your own skin may simply not be enough. Until recently, burns of more than 30% of the body surface were considered lethal. In addition, in some cases, skin rejection occurs during transplantation due to the presence of toxins in it, the release of which accompanies thermal trauma. "We have to cut off the skin from the same area several times," says Irina Shlyk, senior researcher at the Institute of Emergency Medicine.
Scientists of the St. Petersburg Institute of Cytology (INC) RAS has developed cellular products that can be used in the treatment of patients with 98% skin burn. In the spring of last year, a patent was obtained for a new product – the full equivalent of leather. The main advantage of INC technology is that the patient's own skin is not required, its equivalent is grown in advance, in vitro. INC scientists have learned how to grow cells that do not cause rejection.
Scientists have been lucky for the last three decades. In the Soviet years, the Institute of Cytology was equipped according to the most modern standards at that time. In the late 1980s, within the framework of the state defense order, the INC together with the Military Medical Academy named after S.M. Kirov worked on a project under the code "Adamant" - "Biotechnological cultivation of human skin cells for the treatment of critical and supercritical burns." The project lasted nine years (1991-2000), during which the main results were obtained. Since the beginning of the 1990s, scientists have managed to obtain budget grants for research for a considerable amount - 30 million rubles. But in 2007, when it came to bringing the product to market, it seemed to scientists that the streak of relative luck was over.
Therapeutic "sandwich"In the West, the practice of creating spin-offs – private companies at scientific institutions – is very common and is strongly encouraged by governments.
One of the few Russian spin-offs is the Center for Cellular Technologies (CCT) company, established by INC scientists together with specialists in the development of production. CCT appeared in 2005, when it became clear that scientists have a clear product for practical use in clinics. Today it is already a number of cellular products using cultured human skin cells.
The head of the Cell culture Department of the INC, Georgy Pinaev, avoids using the term "stem cells": "This is a completely scientific concept too spoiled by amateurs and dishonest businessmen." But it was Pinaev and his colleagues who were among the first in the USSR to isolate these cells, learn how to multiply, store, and use them. As a result of numerous experiments, cellular products appeared – a layer of keratinocytes, a dermal equivalent and a full skin equivalent (a combination of the first two products, which scientists briefly call a "sandwich").
Cellular products proved to be effective in repairing various skin lesions. For example, instead of a traumatic procedure of transplantation of one's own skin in case of a burn, the surgeon places a dermal equivalent or "sandwich" on the wound. A person can be discharged from the hospital in two to three weeks, depending on the degree of burn. Cellular products were also effective in the treatment of trophic ulcers resulting from diabetes or venous insufficiency, as well as in the treatment of bedsores, fistulas, wounds and ulcers of any origin.
"What kind of product is needed in a particular case is already determined by doctors," says Miralda Blinova, a leading researcher at the INC. If the burn is shallow, a layer of keratinocytes is sufficient, but the dermal equivalent is still used more often. Until quite recently, neither scientists nor surgeons knew how to properly use cellular products. During the clinical trials, over 150 people were treated, and the number of cell products transferred to clinics amounted to about 20 thousand square meters. cm. "Now it is already possible to develop medical regulations together with doctors to create a legal basis for the use of cell products," Pinaev believes.
Two cellular products of CCT – keratinocyte layer and dermal equivalent – have passed all types of tests: technical, toxicological, clinical. They are registered in the State Register of Medical Technologies, and for the first time in Russia official permits for serial production and clinical use have been obtained. Although dozens of institutions are engaged in cell therapy work in Russia, only INC has such permits. This is the main competitive advantage of developers.
The third product – the full equivalent of the skin – is still being prepared for clinical trials. Scientists plan to register the cellular product according to it by 2010.
Burns are critical and not veryThe main source of demand for cellular products is clinics where INC conducted clinical trials (there are about ten of them).
This is understandable: their employees have become familiar with the advantages of the technology in practice. Only one Research Institute of Emergency Medicine declared a desire to receive different cellular products with a total area of 15 thousand sq. cm per year. Another equally important source of demand is the 18th Medical unit (the former LOMO Hospital), where for the first time in the world cellular products are actively used for the healing of trophic ulcers. Little by little, dentists are also beginning to ask for cells. Scientists estimate the total demand of the Northwestern Federal District for cellular products at 300 thousand square meters. cm per year.
"In critical situations, when it comes to life and death, they turn to us immediately," says Miralda Blinova. At the end of 2006, a girl in a car got into a hole filled with boiling water. Two men who rescued her died from their burns, and a girl with a burn of 90% of the body surface ended up in an ambulance research institute. INC produced about 3 sq . m dermal equivalent, and six months later the patient has already been discharged. Subsequently, an even more serious burn – 98% of the skin of a 16-year–old boy - was also eliminated with the participation of INC. Unfortunately, although it is possible to avoid death with the help of cellular products, such patients still have consequences in the form of limited mobility due to the presence of scars.
But even in cases where burns are not so serious, the use of cellular products is of no less social importance. According to Konstantin Krylov, head of the Department of thermal lesions of the Ambulance Research Institute, burns of II and III degrees account for up to 50% of all cases. The causes of these burns are mainly domestic and industrial. It is important for the victims to receive treatment in a short time and return to service as soon as possible. The number of such patients is about 1.5 thousand per year (according to the St. Petersburg Health Committee, about 2.5-3 thousand patients are treated in total per year).
Now treatment in almost all burn centers is paid for by the state, but there is a problem of introducing new technologies. Cellular products have every chance to enter the Medical and Economic standards and the CHI system due to the reduction of the burden on the budget. According to preliminary estimates, due to the use of cellular products, the cost of treatment is reduced from about 100-150 to 50-75 thousand rubles. Among the reasons Krylov calls a reduction in the length of hospital stay (from 28-35 days to two to three weeks) and a lower cost of a course of medications. And in some cases, when the area of the burn is not very large, you can limit yourself to outpatient treatment.
In the case of trophic ulcers, cellular products are used in the complex treatment of the underlying disease – diabetes or chronic venous insufficiency. With traditional treatment, the patient's life is greatly complicated: bandages, which are usually applied to the ulcer, have to be changed every few days. And cellular products can significantly accelerate the tightening of ulcers, which sometimes also interfere with the main treatment. The number of patients with trophic ulcers in St. Petersburg is about 8 thousand people per year.
Calm the heartEven with complete success in the clinic, scientists do not stop there.
The composition of the nutrient medium, the protein substrate, and the cellular composition are constantly being improved. Promising areas are the treatment of periodontal disease and the elimination of scars. A positive clinical effect has been recorded in dentistry – some clinics have ventured to become pioneers. The treatment of scars is more difficult – so far there are only observations. "This area still requires a lot of research. But we are already confident today: it will not get worse," says Blinova. One can only guess which market will open when the first positive results appear.
In parallel with the development of the three main products, Pinaev's laboratory is already working on technologies for restoring bone tissue, cartilage and heart muscle. To do this, other cells of the adult body are studied – osteocytes (bone), chondrocytes (cartilage) and cardiomyocytes (myocardium). What unites them is that they have one source – bone marrow stem cells (the scientific name is mesenchymal cells).
Some progress has already been made in the creation of cellular products for the restoration of the skull bone and tubular bones. The peculiarity of the cranial bone is that when injured, it does not overgrow on its own, special prostheses are required. Animal experiments have shown that with the help of bone marrow cells isolated from the ilium or sternum, it was possible to make the cranial bone recover. INC scientists have come close to clinical trials in this area and have already applied for two patents.
Pinaev and his colleagues are studying the mechanisms of transformation of bone marrow cells into heart muscle cells – myocardium. It has been established that in the case of a heart attack or inflammation of the myocardium, a natural mechanism is triggered: bone marrow cells enter the bloodstream, reach the heart through capillaries and arteries and differentiate into cardiomyocytes, which restore myocardial tissue. However, according to Pinaev, it is still very far from a complete understanding of all the mechanisms, and even more so of their management.
According to the most conservative estimates, it is possible to talk about the appearance of cellular products for the treatment of bones, cartilage and myocardium no earlier than 2014.
At the crossroads"We are constantly bombarded with orders for cellular products," says Pinaev.
Every time scientists have to solve a difficult moral dilemma. Everything that has been delivered to clinics in recent years has been, as they say, passed by the cash register – free of charge within the framework of research contracts. Neither the INC, nor even the CCT yet have the right to produce and sell cellular products: there are no special premises, no license for production. "We work for an idea, not for money," Pinaev admits. In addition, the need to be distracted by production all the time slows down the development of new products. So the idea of allocating a production line to the company "CCT" arose.
Already in 2007, scientists and managers from the CCT developed a clear plan for the development of production. According to the General director of the CCT Vitaly Vengilevsky, the primary task is to create a pilot industrial site. The technology of production in laboratory conditions is far from perfect: the cost is very high, and new problems may be revealed when scaling. Only after two years of regular production work will it be possible to talk about the proven technology and understanding of the economy. At the same time, the presence of a pilot site is important for turning R&D into a final product.
The volume of necessary investments is 20 million rubles. With this money, the CCT plans to create "clean rooms" according to the international GMP standard, which can be licensed and finally begin to supply cellular products to clinics in St. Petersburg. Part of the funds will be used for the purchase of equipment. A necessary condition is that the production should be located on the territory of the INC. The point here is not that someone does not want to "let go" of the technology. Support at the level of the Presidium of the Russian Academy of Sciences in the Soviet years made it possible to equip the INC with infrastructure that can be used for production today – a liquid nitrogen generator, a cryocomplex, washing facilities, etc. "If you create it all over again, it will take hundreds of millions of rubles," explains Vengilevsky.
In addition, the Institute of Cytology will be the main supplier of personnel for the CCT. "Specialists in cell cultures are simply not trained anywhere in Russia," says Pinaev. Both young specialists and scientific supervisors will not be able to be torn between the institute and production. This explains the fact that scientists do not want to sell the technology – no one will be able to use it anyway. "I would like the technology to be used correctly. This requires the participation of the developers themselves," Blinova is sure.
The management of the Institute supports Pinaev and his colleagues in everything. INC is ready to provide the necessary premises for the creation of "clean rooms" and transfer intellectual property to the CCT. When reaching the design capacity, the CCT could produce up to 200 thousand square meters. cm of cellular products per year. In 2011, the revenue could amount to about 30 million rubles. In the future – access to the markets of the Southern Federal District, the Baltic States, Poland, the CIS. This could create demand for an additional 1.5 million sq. cm of cellular products.
The equivalent of innovation policyThe only difference between the CCT team and real businessmen is that they are waiting for the support of the state.
But they can be easily understood. "Private investors have come to us many times," says Pinaev. "But when they hear that the company does not have its own premises and that most of the investments will be directed to an academic institute, interest immediately disappears."
In mid-2007, at a meeting of the St. Petersburg Health Committee, an official decision was made that the city would find an opportunity to finance the enterprise. The Venture Fund of St. Petersburg, which was being formed at that time, was named as a source of investment. However, the VTB management team, which manages the fund's assets, refused to finance the scientists. At the same time, it turned out that the budget of St. Petersburg for 2008 does not provide any money at all to support the INC project. At the same time, the Legislative Assembly and the Committee for Economic Development, Industrial Policy and Trade had letters signed by Governor Valentina Matvienko with instructions to support the project.
The only option that the city was eventually able to offer scientists was to take part in a competition for the St. Petersburg government award for the best innovative project implemented within the cluster. This award was established this year on the wave of officials' enthusiasm for the development of innovations in a cluster way. The ideology of the award was that a group of interconnected enterprises like Silicon Valley or Bangalore in India should be formed around the applicant company (or better yet, that there already was). Also, applicants were invited to compete according to the criteria of budget efficiency (the amount of tax revenues to the city budget) and the number of jobs created. The amount of the award was 9 million rubles – less than half of the needs of the CCT.
CCT has developed a business plan taking into account all the requirements. Looking at their project in a new way, scientists realized that a cluster in the field of cellular biotechnologies has already been formed around the CCT, it is only necessary to pour money into it. The core of this cluster is the Institute of Cytology and the company "CCT". INC is a supplier of fundamental technologies, and CCT is both a pilot site and a serial production. Other members of the cluster are partner clinics (applied research), educational institutions (St. Petersburg State University and St. Petersburg State University), as well as private companies ready to cooperate with the CCT in the supply of consumables and distribution. The calculations showed very solid contributions to the budget.
The results of the competition were announced on December 18. The award was given to a cluster of digital television, among other participants – companies from the fields of instrumentation, medicine and even furniture construction. Without wishing to say anything offensive about some really professional projects, I would like to note the reluctance of officials to support socially significant projects. If the emphasis is on economic efficiency, projects such as CCT, of course, cannot compete. However, they are the ones who require preferential state support. Even the affiliation of the CCT to dual-use technologies does not work. The question arises: should Georgy Pinaev and his colleagues continue to work?
Portal "Eternal youth" www.vechnayamolodost.ru28.01.2009