Why do scientists need hybrid organisms? How artificial organs are grown

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 coated with the patient's own cells," explains Vladimir Porkhanov, chief physician of the Krasnodar Regional Clinical Hospital No. 1.

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 the 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 all scar tissue will be removed, that is, part of the larynx will have to be removed, then a cavity will be released and a trachea will be placed 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 a 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 for research work on the regeneration of respiratory and lung tissues. 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 Sergey Alekseenko, rector of the Kuban State Medical University.

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". It is awarded to the best doctors for outstanding achievements.

B E D E N I E

Organ growing and its alternatives

Many diseases, including those threatening human life, are associated with disorders in the activity of a particular organ (for example, kidney failure, heart failure, diabetes mellitus, etc.). Not in all cases, these disorders can be corrected using traditional pharmacological or surgical interventions.

There are a number of alternative ways to restore organ function to patients in the event of a serious injury:

1) Stimulation of regeneration processes in the body. Except pharmacological effects in practice, the procedure for introducing into the body is usedstem cells, which have the ability to transform into full-fledged functional cells of the body. Positive results have already been obtained in the treatment of various diseases with stem cells, including the most common diseases in society, such as heart attacks, strokes, neurodegenerative diseases, diabetes and others. However, it is clear that such a method of treatment is applicable only to eliminate relatively small damage organs.

2) Replenishment of the functions of organs with the help of devices of non-biological origin. These can be large-sized devices to which patients are connected to certain time(e.g. hemodialysis machines for kidney failure). There are also models of wearable devices, or devices implanted inside the body (there are options to do this, leaving the patient's own organ, however, sometimes it is removed, and the device completely takes over its functions, as in the case of using an artificial heartAbioCor). In some cases, such devices are used while waiting for the appearance of the necessary donor organ. So far, non-biological analogues are significantly inferior in perfection to natural organs.

3) Use of donor organs. Donor organs transplanted from one person to another are already widely and sometimes successfully used in clinical practice. However, this direction faces a number of problems, such as a serious shortage of donor organs, the problem of the rejection of a foreign organ by the immune system, etc. it has not been put into practice. However, research is underway to improve the efficiency of xenotransplantation, for example, through genetic modification.

4) Growing organs. Organs can be grown artificially both in the human body and outside the body. In some cases, it is possible to grow an organ from the cells of the person to whom it is going to be transplanted. A number of methods have been developed for growing biological organs, for example, using special devices working on the principle of a 3D printer. The direction under consideration includes a proposal on the possibility of growing, to replace a damaged human body with a preserved brain, an independently developing organism, a clone - a “plant” (with a disabled ability to think).

Among the listed four options for solving the problem of insufficiency of organ functions, it is their cultivation that may be the most natural way for the body to recover from major injuries.

This text provides information on current advances in the cultivation of biological organs.

ACHIEVEMENTS AND P E R S P E C T I IN S P R E P R E S P E C T I

FOR MEDICINE NEEDS

Tissue cultivation

The cultivation of simple tissues is an already existing and used technology in practice.

Leather

Restoration of damaged areas of the skin is already part of clinical practice. In some cases, methods are used to regenerate the skin of the person himself, for example, the victim of a burn through special effects. This is, for example, developed by R.R. Rakhmatullin bioplastic material hyamatrix 1 , or biocol 2 , developed by a team led by B.K. Gavrilyuk. Special hydrogels are also used to grow skin at the burn site. 3 .

Methods for printing fragments of skin tissue using special printers are also being developed. Such technologies are being created, for example, by developers from the American centers for regenerative medicine AFIRM 4 and WFIRM 5 .

Dr. Jorg Gerlach and colleagues at the Institute for Regenerative Medicine at the University of Pittsburg have invented a skin grafting device that will help people heal faster from burns. varying degrees gravity. Skin Gun sprays on damaged skin the victim's solution with his own stem cells. On the this moment new method treatment is at an experimental stage, but the results are already impressive: severe burns heal in just a couple of days. 6

Bones

A Columbia University team led by Gordana Vunjak-Novakovic obtained from stem cells seeded on a scaffold a bone fragment similar to that of a temporomandibular joint. 7

Scientists of the Israeli company Bonus Biogroup 8 (founder and Executive Director- Shay Meretzky,ShaiMeretzki) develop methods for growing human bone from a patient's adipose tissue obtained through liposuction. The bone grown in this way has already been successfully transplanted into the paw of a rat.

Teeth

Italian scientists fromuniversityofUdinemanaged to show that the population of mesenchymal stem cells obtained from a single adipose tissue cellin vitroeven in the absence of a specific structural matrix or scaffold, it can be differentiated into a tooth germ-like structure. 9

At the University of Tokyo, scientists have grown full-fledged teeth from mouse stem cells, containing dentary bones and connective fibers, and successfully transplanted them into the jaws of animals. 10

cartilage

Specialists from medical center Columbia University Medical Center, led by Jeremy Mao, succeeded in restoring the articular cartilage of rabbits.

First, the researchers removed the cartilage tissue of the shoulder joint from the animals, as well as the layer under it. bone tissue. Then, collagen scaffolds were placed in place of the removed tissues.

In those animals whose scaffolds contained a transforming growth factor, a protein that controls cell differentiation and growth, bone and cartilage tissue on the humerus was re-formed, and movement in the joint was completely restored. 11

A group of American scientists from The University of Texas at Austin has succeeded in creating cartilage tissue with mechanical properties and composition of the extracellular matrix that change in different areas. 12

In 1997, Surgeon Jay Vscanti of main hospital Massachusetts in Boston managed to grow a human ear on the back of a mouse using cartilage cells. 13

Doctors at Johns Hopkins University removed a tumor-affected ear and part of the cranial bone from a 42-year-old woman with cancer. Using cartilage from the chest, skin and blood vessels from other parts of the patient's body, they grew an artificial ear on her arm and then transplanted it into the right place. 14

Vessels

Researchers from the group of Professor Ying Zheng (Ying Zheng) have grown in the laboratory full vessels by learning to manage their growth and form complex structures from them. Vessels form branches, react normally to constricting substances, transporting blood even through sharp corners. 15

Scientists led by Rice University Chair Jennifer West and Baylor College of Medicine (BCM) molecular physiologist Mary Dickinson have found their way to grow blood vessels, including capillaries, using as the base material of polyethylene glycol (PEG), a non-toxic plastic. Scientists have modified PEG to mimic the body's extracellular matrix.

They then combined it with two kinds of cells needed to form blood vessels. Using light to turn PEG polymer strands into a three-dimensional gel, they created a soft hydrogel containing living cells and growth factors. As a result, the scientists were able to observe how the cells slowly form capillaries throughout the gel mass.

To test the new networks of blood vessels, the scientists implanted hydrogels into the corneas of mice, where there is no natural blood supply. The introduction of the dye into the blood of animals confirmed the existence of normal blood flow in the newly formed capillaries. 16

Swedish doctors from the University of Gothenburg, led by Professor Suchitra Sumitran-Holgersson, performed the world's first transplant of a vein grown from a patient's stem cells. 17

Plot iliac vein about 9 centimeters long, obtained from a deceased donor, was purified from donor cells. The girl's stem cells were placed inside the remaining protein scaffold. Two weeks later, an operation was performed to transplant a vein with smooth muscles and endothelium grown in it.

More than a year has passed since the operation, no antibodies to the transplant were found in the patient's blood, and the child's health improved.

muscles

Employees of the Worcester Polytechnic Institute (USA) successfully eliminated a large wound in muscle tissue in mice by growing and implanting microfilaments consisting of a fibrin protein polymer coated with a layer of human muscle cells. 18

Israeli scientists from the Technion-Israel Institute of Technology are investigating the necessary degree of vascularization and tissue organization in vitro to improve the survival and integration of a tissue-engineered vascularized muscle implant in the recipient's body. 19

Blood

Researchers from the Pierre and Marie Curie University in Paris, led by Luc Douay, have successfully tested artificial blood grown from stem cells on human volunteers for the first time in the world.

Each of the participants in the experiment received 10 billion red blood cells, which is equivalent to about two milliliters of blood. The survival rates of the resulting cells were comparable to those of conventional erythrocytes. 20

Bone marrow

Artificial bone marrow intended for productioninvitroblood cells, was first successfully created by researchers at the Chemical Engineering Laboratory of the University of Michigan (universityofMichigan) under the leadership of Nikolai Kotov (NicholasKotov). With its help, it is already possible to obtain hematopoietic stem cells and B-lymphocytes - cells of the immune system that produce antibodies. 21

Growing complex organs

Bladder.

Dr. Anthony Atala and his colleagues at Wake Forest University in the US are growing bladders from patients' own cells and transplanting them into patients. 22 They selected several patients and took a bladder biopsy from them - samples of muscle fibers and urothelial cells. These cells proliferated for seven to eight weeks in petri dishes on a bubble-shaped base. Then the organs grown in this way were sewn into the bodies of patients. Observations of patients over several years showed that the organs functioned safely, without negative effects characteristic of older treatments. In fact, this is the first time that a sufficiently complex organ, rather than simple tissues such as skin and bones, has been artificially grown.invitroand transplanted into a human body. This team is also developing methods for growing other tissues and organs.

Trachea.

Spanish surgeons performed the world's first transplant of a trachea grown from stem cells of a patient, 30-year-old Claudia Castillo. The organ was grown at the University of Bristol using a donor scaffold of collagen fibers. The operation was performed by Professor Paolo Macchiarini from the Hospital Clínic de Barcelona. 23

Professor Macchiarini is actively collaborating with Russian researchers, which made it possible to perform the first operations for transplanting a grown trachea in Russia. 24

kidneys

Advanced Cell Technology reported in 2002 that they had successfully grown a complete kidney from a single cell taken from a cow's ear using cloning technology to obtain stem cells. Using a special substance, the stem cells were turned into kidney cells.

The tissue was grown on a scaffold made from a self-destructing material created at Harvard Medical School and shaped like an ordinary kidney.

The resulting kidneys, about 5 cm long, were implanted in the cow next to the main organs. As a result artificial kidney successfully began to produce urine. 25

Liver

American experts from the Massachusetts General Hospital (Massachusetts General Hospital), led by Korkut Yugun (Korkut Uygun) successfully transplanted several rats with liver grown in the laboratory from their own cells.

The researchers removed the livers from five laboratory rats, cleaned them of host cells, thus obtaining connective tissue scaffolds of organs. The researchers then injected approximately 50 million liver cells from recipient rats into each of the five scaffolds. Within two weeks, a fully functioning liver was formed on each of the cell-populated scaffolds. The lab-grown organs were then successfully transplanted into five rats. 26

Heart

Scientists from the British hospital Heafield, led by Megdi Yakub, for the first time in history, have grown a part of the heart, using stem cells as a "building material". Doctors have grown tissue that works exactly like the heart valves responsible for blood flow in the human body. 27

Scientists from the University of Rostock (Germany) used laser-induced-forward-transfer (LIFT) cellprinting technology to make a “patch” designed for heart regeneration. 28

Lungs

American scientists from Yale University (Yale University), led by Laura Niklason (Laura Niklason) have grown in the laboratory lungs (on a donor extracellular matrix).

The matrix was filled with lung epithelial cells and the inner lining of blood vessels taken from other individuals. Through cultivation in a bioreactor, the researchers were able to grow new lungs, which were then transplanted into several rats.

The organ functioned normally in different individuals from 45 minutes to two hours after transplantation. However, after that, blood clots began to form in the vessels of the lungs. In addition, the researchers recorded the leakage of a small amount of blood into the lumen of the organ. However, for the first time, researchers have been able to demonstrate the potential of regenerative medicine for lung transplantation. 29

Intestines

A group of Japanese researchers from Nara Medical University (NaraMedicaluniversity) under the direction of Yoshiyuki Nakajima (YoshiyukiNakajima) succeeded in creating a mouse intestinal fragment from induced pluripotent stem cells.

Its functional features, the structure of muscles, nerve cells correspond to the usual intestine. For example, it could contract to move food. 30

Pancreas

Researchers at the Israeli Technion Institute, led by Professor Shulamit Levenberg, have developed a method to grow pancreatic tissue containing secretory cells surrounded by a three-dimensional network of blood vessels.

Transplantation of such tissue into diabetic mice resulted in a significant reduction in blood glucose levels in the animals. 31

thymus

Scientists from the University of Connecticut Health Center(USA)developed a method for targeted in vitro differentiation of mouse embryonic stem cells (ESCs) into thymic epithelial progenitor cells (PET), which differentiated into thymus cells in vivo and restored its normal structure. 32

Prostate

Scientists Prof. Gail Risbridger and Dr. Renia Taylor of Melbourne's Monash Institute for Medical Research have become the first to use embryonic stem cells to grow a human prostate in a mouse. 33

Ovary

A team of specialists led by Sandra Carson (Sandracarson) from Brown University managed to grow the first eggs in an organ created in the laboratory: the path from the stage of the “young Graaffian vesicle” to full maturity has been passed. 34

penis, urethra

Researchers from the Wake Forest Institute for Regenerative Medicine (North Carolina, USA), led by Anthony Atala, managed to grow and successfully transplant penises to rabbits. After the operation, the functions of the penises were restored, the rabbits fertilized the females, they had offspring. 35

Scientists at Wake Forest University in Winston-Salem, North Carolina, have grown urethra from patients' own tissues. In the experiment, they helped five teenagers restore the integrity of damaged channels. 36

Eyes, corneas, retinas

Biologists from the University of Tokyo implanted embryonic stem cells into the eye socket of a frog, from which the eyeball was removed. Then the eye socket was filled with a special nutrient medium that provided nutrition to the cells. A few weeks later, the embryonic cells grew into a new eyeball. Moreover, not only the eye was restored, but also vision. The new eyeball has grown together with the optic nerve and feeding arteries, completely replacing the former organ of vision. 37

Scientists from the Sahlgrenska Academy in Sweden (The Sahlgrenska Academy) for the first time successfully cultivated the human cornea from stem cells. This will help to avoid a long wait for a donor cornea in the future. 38

Researchers at the University of California, Irvine, working under the direction of Hans Kairsted (HansKeirstead), grown from stem cells in laboratory conditions an eight-layer retina to help develop transplant-ready retinas for the treatment of blinding conditions such as retinitis pigmentosa and macular degeneration. Now they are testing the possibility of transplanting such a retina in animal models. 39

Nervous tissues

Researchers at the RIKEN Center for Developmental Biology, Kobe, Japan, led by Yoshiki Sasai, have developed a technique for growing the pituitary gland from stem cells,which has been successfully implanted in mice.Scientists solved the problem of creating two types of tissues by influencing mouse embryonic stem cells with substances that create an environment similar to that in which the pituitary gland is formed. developing embryo, and provided an abundant supply of oxygen to the cells. As a result, the cells formed a three-dimensional structure, outwardly similar to the pituitary gland, containing a complex of endocrine cells that secrete pituitary hormones. 40

Scientists from the Laboratory of Cellular Technologies of the Nizhny Novgorod State Medical Academy have managed to grow a neural network, in fact, a fragment of the brain. 41

They grew a neural network on special matrices - multi-electrode substrates that allow recording the electrical activity of these neurons at all stages of growth.

CONCLUSION

The above review of publications shows that there are already significant achievements in the use of organ cultivation to treat people not only with the simplest tissues, such as skin and bones, but also with rather complex organs, such as the bladder or trachea. Technologies for growing even more complex organs (heart, liver, eye, etc.) are still being worked out on animals. In addition to being used in transplantology, such organs can serve, for example, for experiments that replace some experiments on laboratory animals, or for the needs of art (as the above-mentioned J. Vacanti did). Every year new results appear in the field of growing organs. According to the forecasts of scientists, the development and implementation of the technique of growing complex organs is a matter of time, and it is likely that in the coming decades the technique will be developed to such an extent that the cultivation of complex organs will be widely used in medicine, replacing the most common method of transplantation from donors.

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Before proceeding to the discussion of the topic of the article, I want to make a short excursion into what the human body is. This will help to understand how important the work of any link in a complex system of the human body is, what can happen in the event of a failure, and how modern medicine tries to solve problems if any organ fails.

The human body as a biological system

The human body is a complex biological system with a special structure and endowed with specific functions. Within this system, there are several levels of organization. Higher integration is the organismal level. Next in descending order are the systemic, organ, tissue, cellular and molecular levels of organization. The coordinated work of the entire human body depends on the coordinated work of all levels of the system.
If some organ or organ system does not work properly, then the disorders also affect lower levels of organization, such as tissues and cells.

The molecular level is the first building block. As the name implies, the entire human body, like all living things, consists of countless molecules.

The cellular level can be imagined as a diverse composition of molecules that form different cells.

Cells combined into tissues of different morphology and functioning form the tissue level.

Human organs are made up of a variety of tissues. They ensure the normal functioning of any organ. This is the organ level of the organization.

The next level of organization is systemic. Certain anatomically combined organs perform a more complex function. For example, the digestive system, which consists of various organs, ensures the digestion of food entering the body, the absorption of digestion products and the elimination of unused residues.
And the highest level of organization is the organismic level. All systems and subsystems of the body work like a well-tuned musical instrument. The coordinated work of all levels is achieved due to the mechanism of self-regulation, i.e. support at a certain level of various biological indicators. At the slightest imbalance in the work of any level, the human body begins to work intermittently.

What are stem cells?

The term "stem cells" was introduced into science by the Russian histologist A. Maksimov in 1908. Stem cells (SCs) are non-specialized cells. They are also considered as immature cells. They are found in almost all multicellular organisms, including humans. Cells reproduce themselves by dividing. They are able to transform into specialized cells, i.e. various tissues and organs can form from them.

The largest number of SCs in infants and children, in youth, the number of stem cells in the body decreases by 10 times, and by adulthood - by 50 times! A significant decrease in the number of SCs during aging, as well as severe diseases, reduces the body's ability to self-repair. An unpleasant conclusion follows from this: the vital activity of many important systems organs is reduced.

Stem cells and the future of medicine

Medical scientists have long paid attention to the plasticity of SCs and the theoretical possibility of growing various tissues and organs of the human body from them. Work on the study of the properties of SC began in the second half of the last century. As always, the first studies were carried out on laboratory animals. By the beginning of our century, attempts began to use SC for growing human tissues and organs. I want to talk about the most interesting results in this direction.

Japanese scientists in 2004 succeeded in growing capillary blood vessels from SCs in the laboratory.

The following year, American researchers at Florida State University managed to grow brain cells from SCs. Scientists said that such cells are able to implant in the brain, and they can be used in the treatment of diseases such as Parkinson's and Alzheimer's.

In 2006, Swiss scientists from the University of Zurich grew human heart valves in their laboratory. For this experiment, SCs from amniotic fluid were used. Dr. S. Hörstrap believes that this technique could be used to grow heart valves for an unborn baby with heart defects. After birth, the baby can be transplanted with new valves grown from amniotic fluid stem cells.

In the same year, American doctors grew a whole organ in the laboratory - the bladder. SCs were taken from the person for whom this organ was grown. Dr. E. Atala, director of the Institute of Regenerative Medicine, said that cells and special substances are placed in a special form, which remains in the incubator for several weeks. After that, the finished organ is transplanted to the patient. Such operations are now carried out as usual.

In 2007, at the international medical symposium in Yokohama, a report by Japanese experts from the University of Tokyo on an amazing scientific experiment was presented. From a single stem cell taken from the cornea and placed in a nutrient medium, it was possible to grow a new cornea. The scientists intended to start clinical research and further apply this technology in the treatment of eyes.

The Japanese hold the palm in growing a tooth from a single cell. SC was transplanted onto a collagen scaffold and the experiment began. After growing, the tooth looked like a natural one and had all the components, including dentin, vessels, enamel, etc. The tooth was transplanted into a laboratory mouse, and it survived and functioned normally. Japanese scientists see great prospects for using this method in growing a tooth from a single SC, followed by transplanting it into a cell host.

Japanese doctors from the University of Kyoto succeeded in obtaining tissues of the kidneys, adrenal glands and a fragment of the renal tubule from SC.

Every year, millions of people around the world die from diseases of the heart, brain, kidneys, liver, muscular dystrophy etc. Stem cells can help in their treatment. However, there is one thing that can slow down the use of stem cells in medical practice - this is the lack of an international legal framework: where can the material be taken from, how long can it be stored, how should the patient and his doctor interact when using SC.

Probably, the conduct of medical experiments and the development of such a law should go hand in hand.

Medical scientist at work

For many years, scientists around the world have been working on creating working tissues and organs from cells. The most common practice is to grow new tissues from stem cells. This technology has been developed for many years and consistently brings success. But fully ensure required amount organs is not yet possible, since it is possible to grow an organ for a particular patient only from its stem cells.

Scientists from the UK have succeeded in what no one has been able to do so far - to reprogram cells and grow a working organ out of them. This will allow in the foreseeable future to provide organs for transplantation to all who need it.

Growing organs from stem cells

Growing organs from stem cells has been familiar to physicians for a long time. Stem cells are the progenitors of all body cells. They can replace any damaged cells and are intended to restore the body. Maximum amount of these cells occurs in children after birth, and with age their number decreases. Therefore, gradually the body's ability to self-healing is reduced.

Many fully functioning organs from stem cells have already been created in the world, for example, in 2004, capillaries and blood vessels were created from them in Japan. And in 2005, American scientists managed to create brain cells. In 2006, human heart valves from stem cells were created in Switzerland. In the same 2006, liver tissue was created in Britain. Until today, scientists have dealt with almost all tissues of the body, even grown teeth.

A very curious experiment was carried out in the USA - they grew a new heart on a frame from the old one. Donor heart cleared of muscle and built up new muscle from stem cells. This completely eliminates the possibility of rejection of the donor organ, as it becomes "one's own". By the way, there are suggestions that as a frame, it will be possible to use the heart of a pig, which is anatomically very similar to a human one.

A new way to grow organs for transplant (Video)

The main disadvantage of the existing method of growing organs is the need for their production of the patient's own stem cells. Not every patient can take stem cells, and even more so, not everyone has ready-made frozen cells. But recently, researchers from the University of Edinburgh managed to reprogram the cells of the body in such a way that they allow them to grow the necessary organs from them. According to forecasts wide application This technology will be possible in about 10 years.

This article provides information on existing achievements in the cultivation of biological organs.

There are a number of alternative ways to restore organ function to patients in the event of a serious injury:

Stimulation of regeneration processes in the body. In addition to pharmacological effects, practice uses the procedure for introducing stem cells into the body, which have the ability to turn into full-fledged functional cells of the body. Positive results have already been obtained in the treatment of various diseases with stem cells, including the most common diseases in society, such as heart attacks, strokes, neurodegenerative diseases, diabetes and others. However, it is clear that such a method of treatment is applicable only to repair relatively minor damage to organs.
Completion of the functions of organs with the help of devices of non-biological origin. These can be large-sized devices to which patients are connected for a certain time (for example, hemodialysis machines for kidney failure). There are also models of wearable devices, or devices implanted inside the body (there are options to do this, leaving the patient's own organ, however, sometimes it is removed, and the device completely takes over its functions, as in the case of using the AbioCor artificial heart). In some cases, such devices are used while waiting for the appearance of the necessary donor organ. So far, non-biological analogues are significantly inferior in perfection to natural organs.
Use of donor organs. Donor organs transplanted from one person to another are already widely and sometimes successfully used in clinical practice. However, this direction faces a number of problems, such as a serious shortage of donor organs, the problem of the rejection of a foreign organ by the immune system, etc. it has not been put into practice. However, research is underway to improve the efficiency of xenotransplantation, for example, through genetic modification.
Growing organs. Organs can be grown artificially both in the human body and outside the body. In some cases, it is possible to grow an organ from the cells of the person to whom it is going to be transplanted. A number of methods have been developed for growing biological organs, for example, using special devices that work on the principle of a 3D printer. The direction under consideration includes a proposal on the possibility of growing, to replace a damaged human body with a preserved brain, an independently developing organism, a clone - a “plant” (with a disabled ability to think).
Among the listed four options for solving the problem of insufficiency of organ functions, it is their cultivation that may be the most natural way for the body to recover from major injuries.

Achievements and prospects in the cultivation of individual organs for the needs of medicine

Tissue cultivation

Growing simple tissues is a technology that already exists and is used in practice.

Leather

Restoration of damaged areas of the skin is already part of clinical practice. In some cases, methods are used to regenerate the skin of the person himself, for example, the victim of a burn through special effects. This is, for example, developed by R.R. Rakhmatullin bioplastic material hyamatrix, or biocol, developed by a team led by B.K. Gavrilyuk. Special hydrogels are also used to grow skin at the burn site.

Dr. Jorg Gerlach and colleagues at the Institute for Regenerative Medicine at the University of Pittsburg have invented a skin grafting device that will help people heal faster from burns of varying severity. Skin Gun sprays a solution with his own stem cells onto the damaged skin of the victim. At the moment, a new method of treatment is at an experimental stage, but the results are already impressive: severe burns heal in just a couple of days.

Bones

A Columbia University team led by Gordana Vunjak-Novakovic obtained from stem cells seeded on a scaffold a bone fragment similar to that of a temporomandibular joint.

Scientists from the Israeli company Bonus Biogroup (founder and CEO - Pai Meretzki, Shai Meretzki) are developing methods for growing human bone from a patient's adipose tissue obtained through liposuction. The bone grown in this way has already been successfully transplanted into the paw of a rat.

Teeth

Italian scientists from the University of Udine were able to show that a population of mesenchymal stem cells obtained from a single adipose tissue cell in vitro, even in the absence of a specific structural matrix or substrate, can be differentiated into a structure resembling a tooth germ.

cartilage

Specialists from the Columbia University Medical Center (Columbia University Medical Center), led by Jeremy Mao (Jeremy Mao) managed to restore the articular cartilage of rabbits.

First, the researchers removed the cartilage tissue of the shoulder joint from the animals, as well as the underlying layer of bone tissue. Then, collagen scaffolds were placed in place of the removed tissues.

In 1997, Surgeon Jay Vscanti of Massachusetts General Hospital in Boston succeeded in making a human ear on the back of a mouse using cartilage cells.

Vessels

Researchers from the group of Professor Ying Zheng (Ying Zheng) have grown full-fledged vessels in the laboratory, having learned to control their growth and form complex structures from them. Vessels form branches, react normally to constricting substances, transporting blood even through sharp corners.

Scientists led by Rice University Chair Jennifer West and Baylor College of Medicine (BCM) molecular physiologist Mary Dickinson have found their way to grow blood vessels, including capillaries, using as the base material of polyethylene glycol (PEG) - a non-toxic plastic. Scientists have modified PEG to mimic the body's extracellular matrix.

Swedish doctors from the University of Gothenburg, led by Professor Suchitra Sumitran-Holgersson, performed the world's first transplant of a vein grown from a patient's stem cells.

A section of the iliac vein about 9 centimeters long, obtained from a deceased donor, was cleared of donor cells. The girl's stem cells were placed inside the remaining protein scaffold. Two weeks later, an operation was performed to transplant a vein with smooth muscles and endothelium grown in it.

More than a year has passed since the operation, no antibodies to the transplant were found in the patient's blood, and the child's health improved.

muscles

Researchers at the Worcester Polytechnic Institute (USA) successfully repaired a large wound in muscle tissue in mice by growing and implanting microfilaments consisting of a protein polymer fibrin coated with a layer of human muscle cells.

Blood

Researchers from the Pierre and Marie Curie University in Paris, led by Luc Douay, have successfully tested artificial blood grown from stem cells on human volunteers for the first time in the world.

Bone marrow

An artificial bone marrow designed for the in vitro production of blood cells has been successfully created for the first time by researchers at the University of Michigan Chemical Engineering Laboratory led by Nicholas Kotov. With its help, it is already possible to obtain hematopoietic stem cells and B-lymphocytes - cells of the immune system that produce antibodies.

Growing complex organs

Bladder

Dr. Anthony Atala and his colleagues at Wake Forest University in the US are growing bladders from patients' own cells and transplanting them into patients. They selected several patients and took a bladder biopsy from them - samples of muscle fibers and urothelial cells. These cells proliferated for seven to eight weeks in petri dishes on a bubble-shaped base. Then the organs grown in this way were sewn into the bodies of patients. Follow-ups of patients over several years showed that the organs functioned well, without the negative effects of older treatments. In fact, this is the first time that a sufficiently complex organ, rather than simple tissues such as skin and bones, has been artificially grown in vitro and transplanted into a human body. This team is also developing methods for growing other tissues and organs.

Trachea

Professor Macchiarini is actively collaborating with Russian researchers, which made it possible to perform the first operations for transplanting a grown trachea in Russia.

kidneys

The tissue was grown on a scaffold made from a self-destructing material created at Harvard Medical School and shaped like an ordinary kidney.

The resulting kidneys, about 5 cm long, were implanted in the cow next to the main organs. As a result, the artificial kidney successfully began to produce urine.

Liver

Heart

Scientists from the University of Rostock (Germany) used laser-induced-forward-transfer (LIFT) cellprinting technology to make a “patch” designed for heart regeneration.

Lungs

American scientists from Yale University (Yale University), led by Laura Niklason (Laura Niklason) have grown in the laboratory lungs (on a donor extracellular matrix).

Intestines

A group of Japanese researchers at Nara Medical University, led by Yoshiyuki Nakajima, have succeeded in creating a mouse intestinal fragment from induced pluripotent stem cells.

Its functional features, the structure of muscles, nerve cells correspond to the usual intestine. For example, it could contract to move food.

Pancreas

Transplantation of such tissue into diabetic mice resulted in a significant reduction in blood glucose levels in the animals.

thymus

Scientists from the University of Connecticut Health Center (USA) have developed a method for directed in vitro differentiation of mouse embryonic stem cells (ESCs) into thymic epithelial progenitor cells (PET), which differentiated into thymus cells in vivo and restored its normal structure.

Prostate

Scientists Prof. Gail Risbridger and Dr. Renia Taylor of Melbourne's Monash Institute for Medical Research have become the first to use embryonic stem cells to grow a human prostate in a mouse.

Ovary

A team of specialists led by Sandra Carson of Brown University managed to grow the first eggs in a laboratory-created organ, going from a “young Graaffian vesicle” to full maturity.

penis, urethra

Eyes, corneas, retinas

Scientists from The Sahlgrenska Academy in Sweden have successfully cultured the human cornea from stem cells for the first time. This will help to avoid a long wait for a donor cornea in the future.

Researchers at the University of California at Irvine, led by Hans Keirstead, have grown eight-layer retinas from stem cells in the lab, which will help develop transplant-ready retinas for the treatment of blinding conditions such as retinitis pigmentosa and macular degeneration. Now they are testing the possibility of transplanting such a retina in animal models.

Nervous tissues

Researchers at the RIKEN Center for Developmental Biology, Kobe, Japan, led by Yoshiki Sasai, have developed a technique for growing the pituitary from stem cells that have been successfully implanted in mice. Scientists solved the problem of creating two types of tissue by exposing mouse embryonic stem cells to substances that create an environment similar to that in which the pituitary gland of a developing embryo is formed, and provided an abundant supply of oxygen to the cells. As a result, the cells formed a three-dimensional structure, outwardly similar to the pituitary gland, containing a complex of endocrine cells that secrete pituitary hormones.

Scientists from the Laboratory of Cellular Technologies of the Nizhny Novgorod State Medical Academy have managed to grow a neural network, in fact, a fragment of the brain.

They grew a neural network on special matrices - a lot of electrode substrates that allow you to record the electrical activity of these neurons at all stages of growth.

Conclusion

The above review of publications shows that there are already significant achievements in the use of growing organs for treating people not only with the simplest tissues, such as skin and bones, but also with rather complex organs, such as the bladder or trachea. Technologies for growing even more complex organs (heart, liver, eye, etc.) are still being worked out on animals. In addition to being used in transplantology, such organs can serve, for example, for experiments that replace some experiments on laboratory animals, or for the needs of art (as the above-mentioned J. Vacanti did). Every year new results appear in the field of growing organs. According to the forecasts of scientists, the development and implementation of the technique of growing complex organs is a matter of time, and it is likely that in the coming decades the technique will be developed to such an extent that the cultivation of complex organs will be widely used in medicine, replacing the most common method of transplantation from donors.