How are artificial organs grown? Growing Organs
21/06/2017
Artificial organ farming could save millions of lives. Regularly coming news from the field of regenerative medicine sounds encouraging and promising. It seems that the day is not far off when bioengineered tissues and organs will be as available as car parts.
Advances in regenerative medicine
Methods of therapy using cellular technologies have been successfully used in medical practice for many years. Created and successfully used artificial organs and tissues obtained using methods of cell therapy and tissue engineering. Practical achievements in the field of regenerative biomedicine include the cultivation of cartilage tissues, Bladder, urethra, heart valves, trachea, cornea and skin. Managed to grow artificial tooth, so far only in the body of a rat, but dentists should think about radically new approaches. A technology has been developed to restore the larynx after surgery to remove it, and many such operations have already been performed. Known cases successful implantation trachea grown on a donor matrix from the patient's cells. Artificial cornea transplantation has been carried out for many years.
Serial production of bioprinters has already been launched, which, layer by layer, print living tissues and organs of a given three-dimensional shape.
The easiest to grow were cartilage tissue and skin. Much progress has been made in growing bones and cartilage on matrices. Next level occupied by blood vessels. At the third level were the bladder and uterus. But this stage has already been passed in 2000-2005, after the successful completion of a number of operations for transplantation of an artificial bladder and urethra. Tissue implants of the vagina, grown in the laboratory from muscle and epithelial cells of patients, not only successfully took root, forming nerves and blood vessels, but also function normally for about 10 years.
The most complex organs for biomedicine remain the heart and kidneys, which have a complex innervation and system. blood vessels. Growing a whole artificial liver is still a long way off, but fragments of human liver tissue have already been obtained using the method of growing on a matrix of biodegradable polymers. And although the successes are obvious, the replacement of such is vital important organs, like the heart or liver, their grown counterparts are still a matter of the future, although, perhaps, not very distant.
Matrices for organs
Non-woven sponge matrices for organs are made from biodegradable polymers of lactic and glycolic acids, polylactone and many other substances. There are also great prospects for gel-like matrices, into which, in addition to nutrients, growth factors and other inducers of cell differentiation can be introduced in the form of a three-dimensional mosaic corresponding to the structure of the future organ. And when this organ is formed, the gel dissolves without a trace. To create a scaffold, polydimethylsiloxane is also used, which can be populated with cells of any tissue.
The basic technology for growing organs, or tissue engineering, is to use embryonic stem cells to obtain specialized tissues.
The next step is lining inner surface polymer by immature cells, which then form the walls of blood vessels. Further, other cells of the desired tissue, as they multiply, will replace the biodegradable matrix. The use of a donor scaffold that determines the shape and structure of the organ is considered promising. In the experiments, the rat heart was placed in a special solution, with which cells of the muscle tissue of the heart were removed, leaving other tissues intact. The purified scaffold was seeded with new cardiac muscle cells and placed in a medium that mimics the conditions in the body. In just four days, the cells had multiplied enough to start contracting the new tissue, and eight days later, the reconstructed heart was pumping blood. The same method was used to grow on a donor framework new liver, which was then transplanted into the body of a rat.
Basic Organ Growing Technology
Perhaps there is not a single biological tissue that has not been attempted to be synthesized. modern science. The basic technology for growing organs, or tissue engineering, is to use embryonic stem cells to obtain specialized tissues. These cells are then placed within a connective intercellular tissue structure composed predominantly of collagen protein.
A collagen matrix can be obtained by purifying cells from donor biological tissue or creating it by artificial means from biodegradable polymers or special ceramics, if we are talking about bones. In addition to cells, the matrix is injected nutrients and growth factors, after which the cells form a whole organ or its fragment. In the bioreactor, it was possible to grow muscle tissue with a ready-made circulatory system.
The most complex organs for biomedicine remain the heart and kidneys, which have a complex innervation and system of blood vessels.
Human embryonic stem cells were induced to differentiate into myoblasts, fibroblasts, and endothelial cells. Growing along the matrix microtubules, endothelial cells formed capillary beds, came into contact with fibroblasts and forced them to regenerate into smooth muscle tissue. Fibroblasts secreted vascular endothelial growth factor, which contributed to further development blood vessels. When transplanted into mice and rats, such muscles took root much better than tissue sections consisting of muscle fibers alone.
Organelles
Using three-dimensional cell cultures, it was possible to create a simple, but quite functional liver person. In a joint culture of endothelial and mesenchymal cells, when a certain ratio is reached, their self-organization begins and three-dimensional spherical structures are formed, which are the liver germ. 48 hours after transplantation of these fragments into mice, connections with blood vessels are established, and the implanted parts are able to perform functions characteristic of the liver. Successful experiments on the implantation of a lung grown on a donor matrix purified from cells have been carried out in rats.
By influencing the signaling pathways of induced pluripotent stem cells, it was possible to obtain human lung organelles consisting of epithelial and mesenchymal compartments with structural features characteristic of lung tissue. Bioengineered submandibular embryos salivary glands, constructed in vitro, after transplantation, are able to develop into a mature gland by the formation of pampiniform processes with muscle epithelium and innervation.
3D organelles of the eyeball and retina with photoreceptor cells: rods and cones have been developed. An eyeball was grown from undifferentiated frog embryonic cells and implanted into the eye cavity of a tadpole. A week after the operation, there were no symptoms of rejection, and the analysis showed that the new eye was fully integrated into nervous system and is capable of transmitting nerve impulses.
And in 2000, data on the creation of eyeballs grown from undifferentiated embryonic cells. cultivation nervous tissue the most difficult because of the variety of types of its constituent cells and their complex spatial organization. However, to date, there is a successful experience of growing the adenohypophysis of the mouse from the accumulation of stem cells. A three-dimensional culture of brain cell organelles obtained from pluripotent stem cells has been created.
printed organs
Serial production of bioprinters has already been launched, which, layer by layer, print living tissues and organs of a given three-dimensional shape. The printer is capable of applying living cells at high speed to any suitable substrate, which is a thermoreversible gel. At temperatures below 20 °C, it is a liquid, and when heated above 32 °C, it solidifies. Moreover, printing is carried out "from the customer's material", that is, from solutions of living cell cultures grown from the patient's cells. The cells sprayed by the printer grow together after a while. The thinnest layers of gel give strength to the structure, and then the gel can be easily removed with water. However, in order to be able to form a functioning organ containing cells of several types in this way, a number of difficulties must be overcome. The control mechanism by which dividing cells form the correct structures is not yet fully understood. However, it seems that despite the complexity of these tasks, they are still solvable and we have every reason to believe in the rapid development of a new type of medicine.
Biosafety of the use of pluripotent cells
A lot is expected from regenerative medicine, and at the same time, the development of this area gives rise to many moral, ethical, medical and regulatory issues. A very important issue is the biosafety of the use of pluripotent stem cells. We have already learned how to reprogram blood and skin cells with the help of transcription factors into induced pluripotent stem cells. The resulting cultures of the patient's stem cells can later develop into neurons, tissues skin, blood and liver cells. It should be remembered that in adults healthy body there are no pluripotent cells, but they can spontaneously arise in sarcoma and teratocarcinoma. Accordingly, if pluripotent cells or cells with induced pluripotency are introduced into the body, they can provoke the development malignant tumors. Therefore, full confidence is needed that the biomaterial transplanted to the patient does not contain such cells. Technologies are now being developed that allow direct production of tissue cells of a certain type, bypassing the state of pluripotency.
In the 21st century With the development of new technologies, medicine must move to a qualitatively new level, which will allow timely "repair" of the body affected by a serious illness or age-related changes. I would like to believe that very soon growing organs directly in the operating room from the patient's cells will be as easy as flowers in greenhouses. The hope is reinforced by the fact that tissue-growing technologies are already working in medicine and saving lives.
Post-industrial rates of development of mankind, namely science and technology, are so great that they could not be imagined 100 years ago. What used to be read only in popular science fiction has now appeared in the real world.
The level of development of medicine in the 21st century is higher than ever. Diseases that were considered deadly in the past are successfully treated today. However, the problems of oncology, AIDS and many other diseases have not yet been solved. Fortunately, in the near future there will be a solution to these problems, one of which will be the cultivation of human organs.
Fundamentals of bioengineering
Science, using the informational basis of biology and using analytical and synthetic methods to solve its problems, originated not so long ago. Unlike conventional engineering, which uses technical sciences, mostly mathematics and physics, for its activities, bioengineering goes further and uses innovative methods in the form of molecular biology.
One of the main tasks of the newly minted scientific and technical sphere is the cultivation of artificial organs in laboratory conditions for the purpose of their further transplantation into the body of a patient whose organ has failed due to damage or deterioration. Based on three-dimensional cell structures, scientists were able to advance in the study of the influence of various diseases and viruses on the activity of human organs.
Unfortunately, so far these are not full-fledged organs, but only organelles - rudiments, an unfinished collection of cells and tissues that can only be used as experimental samples. Their performance and livability are tested on experimental animals, mainly on different rodents.
History reference. transplantology
The growth of bioengineering as a science was preceded by long period development of biology and other sciences, the purpose of which was to study human body. As early as the beginning of the 20th century, transplantation received an impetus to its development, the task of which was to study the possibility of transplanting a donor organ to another person. The creation of methods capable of preserving donor organs for some time, as well as the availability of experience and detailed plans for transplantation, allowed surgeons from all over the world to successfully transplant organs such as the heart, lungs, and kidneys in the late 60s.
On the this moment The principle of transplantation is most effective when the patient is in mortal danger. The main problem lies in acute shortage donor organs. Patients can wait for their turn for years, without waiting for it. In addition, there is high risk the fact that a transplanted donor organ may not take root in the body of the recipient, since immune system patient, he will be treated as foreign object. In opposition to this phenomenon, immunosuppressants were invented, which, however, cripple rather than cure - human immunity is catastrophically weakening.
Advantages of artificial creation over transplantation
One of the main competitive differences between the method of growing organs and transplanting them from a donor is that, under laboratory conditions, organs can be produced on the basis of tissues and cells of the future recipient. Basically, stem cells are used, which have the ability to differentiate into cells of certain tissues. This process the scientist is able to control from the outside, which significantly reduces the risk of future rejection of the organ by the human immune system.
Moreover, with the help of the method of artificial organ cultivation, it is possible to produce an unlimited number of them, thereby satisfying the vital needs of millions of people. The principle of mass production will significantly reduce the price of organs, saving millions of lives and significantly increasing human survival and pushing back the date of its biological death.
Achievements in bioengineering
To date, scientists are able to grow the rudiments of future organs - organelles on which they test various diseases, viruses and infections in order to trace the infection process and develop countermeasures. The success of the functioning of organelles is checked by transplanting them into the bodies of animals: rabbits, mice.
It is also worth noting that bioengineering has achieved some success in creating full-fledged tissues and even in growing organs from stem cells, which, unfortunately, cannot yet be transplanted to a person due to their inoperability. However, at the moment, scientists have learned how to artificially create cartilage, blood vessels and other connecting elements.
Skin and bones
Not so long ago, scientists at Columbia University managed to create a bone fragment similar in structure to a joint. mandible connecting it to the base of the skull. The fragment was obtained through the use of stem cells, as in the cultivation of organs. A little later, the Israeli company Bonus BioGroup managed to invent new method recreation human bone, which was successfully tested on a rodent - an artificially grown bone was transplanted into one of its paws. AT this case again, stem cells were used, only they were obtained from the patient's adipose tissue and subsequently placed on a gel-like bone framework.
Since the 2000s, doctors have been using specialized hydrogels and methods of natural regeneration of damaged skin to treat burns. Modern experimental techniques make it possible to cure severe burns in a few days. The so-called Skin Gun sprays a special mixture with the patient's stem cells onto the damaged surface. There are also major advances in creating stable functioning skin with blood and lymph vessels.
Recently, scientists from Michigan managed to grow in the laboratory part muscle tissue, which, however, is twice as weak as the original. Similarly, scientists in Ohio created three-dimensional stomach tissues that were able to produce all the enzymes needed for digestion.
Japanese scientists have done the almost impossible - they have grown a fully functioning human eye. The problem with transplantation is what to attach optic nerve eyes to the brain is not yet possible. In Texas, it was also possible to grow lungs artificially in a bioreactor, but without blood vessels, which casts doubt on their performance.
Development prospects
It will not be long before the moment in history when it will be possible to transplant most of the organs and tissues created in artificial conditions. Already, scientists from all over the world have developed projects, experimental samples, some of which are not inferior to the originals. Skin, teeth, bones, everything internal organs after some time, it will be possible to create in laboratories and sell to people in need.
New technologies are also accelerating the development of bioengineering. 3D printing, which has become widespread in many areas of human life, will also be useful in growing new organs. 3D bioprinters have been experimentally used since 2006, and in the future they will be able to create 3D workable models of biological organs by transferring cell cultures to a biocompatible basis.
General conclusion
Bioengineering as a science, the purpose of which is the cultivation of tissues and organs for their further transplantation, was born not so long ago. The leaping pace at which it is making progress is characterized by significant achievements that will save millions of lives in the future.
Bones and internal organs grown from stem cells will eliminate the need for donor organs, the number of which is already in short supply. Already, scientists have a lot of developments, the results of which are not very productive yet, but have great potential.
Researchers have overcome the barrier in creating artificial sperm. Synthetic people become a reality?
Scientists have come close to recreating the natural process by which the body creates sperm from stem cells. The study was part of a work that could eventually provide new treatments for infertility.
Speaking at the Progress Education Trust's annual conference in London, Azeem Surani, head of the study, said he and his colleagues have passed a milestone on the path to sperm production in the lab. The team is believed to be half way through the development of stem cells to immature sperm cells.
The study hints that one day it will be possible to produce sperm and eggs from stem cells or from the same skin cells, thank you.
Previously, scientists used stem cells to create viable mouse sperm, which was then used to produce healthy offspring.
We cannot be absolutely sure that the new cells are full-fledged spermatozoa. Lab chambers have development timers, so you must let them develop according to their internal time. Azim Surani, head of research.
There are concerns about the use of artificially created sperm and eggs, as any genetic flaws are potentially passed on to all future generations. What is insignificant, with the development and approval of technology.
Surani's team is trying to closely track the long developmental journey that takes place in the body. The main problem is the timing of cell development. If in mice the process takes place in a few weeks, with a person everything is much more complicated.
In a recent study, his team showed they could reach the roughly four-week mark of human sperm development. But scientists are aiming to extend this to an eight-week stage of distinct cell formation.
To that end, the team has developed miniature artificial eggs called gonadal organelles, which contain gonadal cells (also grown in the lab) encapsulated in a gel.
The DNA in germ cells must go through a process known as erasure. Getting rid of chemical marks that have been built into parental DNA through exposure environment. Most of these so-called epigenetic markers are cleared immediately after fertilization of the egg. This limits the degree of influence life experience parents on the biology of children. However, the second, more thorough, data reset occurs when the embryonic stem cells turn into an egg or sperm.
The problem now is to make sure that laboratory-grown sperm and eggs exactly follow the developmental path of the body's natural cells. With the successful overcoming of the problem, artificial cells will become available for solving problems with infertility, or for the full-fledged cultivation of artificial people.
Improving the state of human health, saving life, increasing its duration - these issues were, are and will be the most relevant for humanity. That is why the theme of cultivation artificial organs in Russia in 2018 occupies the minds of Russian scientists, is on the agenda of the Ministry of Health and is widely discussed in the media.
Gives great hope that the industry scientific medicine- bioengineering technologies will finally have a full-fledged legislative basis. This will enable development, preclinical and clinical researches, practically use cell products, guided and based on the regulatory framework.
Biomedical Cell Products Law
The main thing for scientists and physicians is that in Russia since January 2017 the law “On biomedical cell products».
It was developed as part of the implementation of the strategy for the development of science in Russian Federation until 2025 and is aimed at regulating relations in connection with the development, research, registration, production and quality control, application in medical practice biological medical cell products (BMCP).
Also, this law will provide a legislative basis for the creation of a new industry in the healthcare sector, which, by the production and use of a cellular product, will solve the problems of restoring the functions and structures of human body tissues damaged by diseases, injuries, disorders during fetal development.
main goal federal law is to consolidate a separate settlement of the BMCP circulation activity, which until recently was fragmented, incomplete and mostly illegal.
Now organizations and enterprises that dealt with bioproducts illegally are paralyzed. That is why the adoption of the law was resisted and many obstacles were created. Negative consequences only those who carried out activities in the field of application of cellular material illegally, that is, violated the law, will feel from the adoption of the law.
For the industry as a whole, the law provides civilized ways of development, expansion of opportunities, and for patients it guarantees a high-quality, safe product.
A new era in medicine
Together with research and development effective methods treatment and restoration of the human body, Russian medicine is actively working on the creation of artificial organs. This topic began to be dealt with more than fifty years ago, from the time when the technique of transplanting donor organs passed from theory into practice.
Donation has saved many lives, but this method has a significant number of problems - lack of donor organs, incompatibility, rejection by the immune system. Therefore, the idea of growing artificial organs was enthusiastically picked up by medical scientists around the world.
The method of replacing damaged tissues with an artificial cellular product introduced from the outside, or by activating one's own cells, is based on the viability of BMCT and the ability to permanently reside in the patient's body. This provides great opportunities for effective treatment of diseases and saving many lives.
To date, the use of bioengineering technologies in medicine has achieved significant results. Methods for growing some organs directly in the human body and outside the body have already been tested. It is possible to grow an organ from the cells of the person to whom it will subsequently be implanted.
The use of artificially created simple tissues is already taking place in clinical practice. According to Yuri Sukhanov, executive director Associations of experts in biomedical cell technologies and regenerative medicine, Russian scientists have prepared a number of important and necessary products for testing.
“These are cancer vaccines based on living human cells, drugs for the treatment of diabetes using insulin-producing cells, which will be implanted in the patient. Of course the skin - burns, wounds, diabetic foot. Growing from cartilage, skin, cornea, urethra cells. And, of course, cellular vaccines are the most interesting and effective thing that exists now,” said Yuri Sukhanov.
Russian scientists have created an artificial liver and conducted preclinical tests of the product on animals, which showed very nice results. An element of the grown organ was implanted in damaged tissues animal liver.
As a result, artificial liver cells contributed to tissue regeneration, and after a while the damaged organ was completely restored. This did not happen negative influence on the life span of the experimental animal.
Regenerative medicine is our future, which is being laid today. Her possibilities are enormous. Especially since traditional medicine has reached a certain level, and now cannot offer effective methods treatment of many dangerous diseases that claim millions of lives.
Medical science needs a revolution, a powerful breakthrough, which will be the advent of cellular technologies. win incurable diseases reduce the duration and cost of treatment, make it affordable to replace a lost or non-viable organ and thus save and prolong life - all this gives us a new promising industry medical science- tissue engineering.
The Law “On Biomedical Cellular Products”, adopted in 2017, began to fully work. And now scientists have much more opportunities for new research and discoveries in the field of cell technologies and the cultivation of artificial organs in Russia.
The first operation to transplant organs from the cells of the patient himself will take place in Krasnodar, and now the last preparations for it are being completed. In total, two such transplantations have been carried out in the world, while for Russian surgeons this is the first experience. Previously, only donor organs were transplanted in the country.
"This is an artificially grown trachea, which will also be applied with the patient's own cells," explains chief physician Krasnodar Regional clinical hospital No. 1 Vladimir Porkhanov.
The framework for the future organ was constructed in the American and Swedish laboratories from a nanocomposite material.
This is an exact copy of the trachea of a patient who needs surgery. Outwardly, it looks like a tube made of elastic porous plastic, on which doctors plant the patient's own cells isolated from bone marrow. In 2-3 days, the base of the trachea is formed. The patient's body not only does not reject it, but on the contrary, the transplanted organ itself begins to adapt to the new conditions.
“Then the cells will differentiate, create their own microenvironment, produce tissue. After all, a cell, when alive, many processes take place in it. This will take place in your body,” says transfusiologist, employee of the cultivation laboratory of the Krasnodar Regional Clinical Hospital No. 1 Irina Gilevich.
Paolo Macchiarini is studying the course of a future operation with the surgeons of the Krasnodar hospital point by point. He is the author of a technique for transplanting an artificially grown trachea. The first operation was carried out last year in Sweden. It lasted 12 hours. How long this transplantation will take, the doctors do not say. After all, for the first time in the world, not only an artificial trachea, but also part of the larynx will be transplanted.
"During the operation, an excision will be performed and the entire scar tissue, that is, it will be necessary to remove part of the larynx, then the cavity will be released and put the trachea in this place. It is very difficult, because next to vocal cords", - explains Paolo Macchiarini, professor of regenerative surgery at the Karolinska Institute (Sweden).
Artificial organs will be transplanted to two patients. These are people who received tracheal injuries several years ago. During this time, he underwent many operations, after which there was no improvement. Transplantation for such patients is the only chance for recovery and full life.
So far, the life of patients is scheduled and mainly consists of prohibitions: you can’t swim, you can’t talk and even laugh. The airways are open, there is a tracheostomy in the throat - a special tube through which patients are now breathing.
“After this operation, the patient will be able to speak and breathe calmly on her own,” says Paolo Macchiarini.
In the future, scaffolds for artificial organs are planned to be created in Russia as well. Professor Macchiarini, together with the Kuban Medical University, won a government mega-grant to conduct research work for tissue regeneration respiratory tract and easy. Now a laboratory is being built on the territory of the university, in which scientists will study the mechanisms of regeneration.
“Here they will work out methods and technologies for cell isolation, seeding cells on these scaffolds, growing cells and working out scientific moments,” says the rector of the Kuban State medical university Sergey Alekseenko.
The results of scientists' research will make life easier for seriously ill people, they no longer have to wait for a suitable donor. In the future, scientists plan to use a similar technique when transplanting skin, artificial arteries, heart valves and more complex organs.
In a day medical worker, which is celebrated today, at 17:20 Channel One will show the ceremony of presenting the national award "Vocation". She is awarded the best doctors for outstanding achievement.
