Important scientific news: biologists from Tufts University (USA) managed to restore the ability to regenerate tail tissue in tadpoles. Such work could be considered ordinary, if not for one circumstance: the result was achieved in a non-trivial way, using optogenetics, which is based on controlling cell activity using light.
The ultimate goal of all such research is to discover the natural mechanisms that control the restoration of body parts and learn how to turn them on in humans. Tadpoles are ideally suited for this task, since at an early stage of development they retain the ability to replace lost limbs, but then abruptly lose it. If you cut off the tail of individuals who have entered the so-called refractory period, they will no longer be able to regrow it.
The internal systems that control regeneration are still present in their body, but for some reason they are stopped. Michael Levin and his colleagues made them work again, essentially turning back physiological time.
It's remarkable how they did it. One group of tailless tadpoles was raised in a container exposed to short flashes of light for two days; the other lived in complete darkness. As a result, the tadpoles of the first group regained full tail tissue, including the structures of the spine, muscles, nerve endings and skin. The second tadpoles were unable to overcome the consequences of amputation, as befits their age.
If it looks like a trick, it's only partly. To understand why this happened, it is necessary to explain the principle underlying the experiment. Indeed, all animals at the same life cycle stage were subjected to identical manipulations. The only thing that distinguished the two groups was the presence or absence of lighting. However, light was not the true cause of the changes that occurred. It served as a remote switch that activated a factor that (in an unclear way) started the regeneration process. Hyperpolarization of transmembrane potentials of cells acted as such a factor; or more simply – bioelectricity.
Optogenetics makes it possible to construct an experiment relatively simply. The mRNA molecules of the light-sensitive protein archerchodopsin were injected into tadpoles. This led to the fact that after some time, “pump proteins” appeared on the surface of ordinary cells located in the thickness of the tissue. When stimulated by light (and only in this case), they induced a current of ions through the membrane, thereby changing its electrical potential.
Essentially, other than light-activated membrane pumps, scientists have offered nothing to help tadpoles. However, just influencing the electrical properties of cells was enough to trigger a complex cascade of regenerative processes in the body. In turn, thanks to optogenetics, inducing these changes from the outside is as easy as shelling pears; you just need to shine the light on the tadpole.
Regeneration remains one of the main mysteries of biology. In 2005, Science magazine listed the following question as one of the 25 most important issues facing science: What Controls Organ Regeneration? Unfortunately, scientists have not yet been able to fully understand why some animals, at any stage of their lives, freely restore lost body parts, while others lose this ability forever. Once upon a time, your body knew how to grow an eye or an arm.
This was a long time ago, at the very beginning of life as an embryo. Specialists are interested in where this knowledge disappears and whether it can be revived again in an adult. Currently, most biologists' searches focus primarily on gene expression or chemical signals. Michael Levin's lab hopes to find the answer to the regeneration mystery in another phenomenon, bioelectricity, and these hopes appear to be well founded.
The fact that electric currents are present in a living organism has been known since Galvani’s experiments. However, few have studied their influence on development as closely as Lewin has. Bioelectricity has long had a chance to become a worthy topic of experimentation, but the molecular revolution in biology in the second half of the twentieth century pushed research interest in this issue to the periphery of science.
Levin, coming from the field of computer modeling and genetics, using the most modern methods that were absent from his predecessors, actually returns this direction to the biological mainstream. At the heart of his enthusiasm is the belief that electricity is a basic physical phenomenon, and evolution could not help but involve it in fundamental processes such as the development of organisms.
By changing the transmembrane potential of the cells, the scientist can instruct the tadpole's tissues to grow an eye in a predetermined area of the body. On the wall of his laboratory hangs a photograph of a six-legged frog. She acquired additional limbs solely as a result of exposure to electrical biocurrents. Unlike neurons, ordinary cells are not capable of firing, but can transmit signals sequentially throughout almost the entire body through gap junctions. If the tail part of a planaria, a tiny worm that can regenerate, is cut off, a request from the area of the cut will go to the head to make sure that it is in place. Block the transmission of this information, and a head will grow instead of a tail.
By manipulating various ion channels that determine the electrical properties of cells, scientists in their experiments produced worms with two heads, two tails, and even an unusual design of worms with four heads. Levin says he was almost always told his ideas wouldn't work. He relied on his intuition, and in most cases it did not fail.
These attempts are still very far from complete knowledge of how to restore a limb in a person. For now, people with disabilities can only rely on improved prostheses. However, a unique laboratory at Tufts University is looking for something even more fundamental: like the genetic code, Levine believes, there must be a bioelectrical code that links membrane voltage gradients and dynamics to anatomical structures.
Having understood it, it will be possible not only to control regeneration, but also to influence the growth of tumors. Levin views them as a consequence of the loss of information about the shape of the body by cells, and the study of cancer is one of the tasks of his laboratory. As is often the case, seemingly different processes can have the same nature.
If the bioelectric code really is behind the construction of various organs of the body, its solution could shed light on two of the most important problems facing humanity.
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Regeneration can be physiological reparative And pathological. The regeneration process is very close, in fact identical to the hyperplastic process (reproduction of cells and intracellular structures). They differ in that hyperplasia (hypertrophy) usually occurs due to the need to enhance function, and regeneration - with the “goal” of normalizing function when an organ is damaged and part of its mass is lost. Previously, it was believed that regeneration was limited only to the organ and tissue levels. It has now become obvious that physiological and reparative regeneration is a universal phenomenon, characteristic not only of the tissue and cellular levels, but also of the intracellular level, including the molecular one (regeneration of damaged DNA structure). Thus, after a pathogenic effect and damage to DNA, it is “healed”, carried out by the sequential work of repair enzymes. They “recognize” the damaged area, expand it, i.e. as if they clean the site of damage, and then “build up” the resulting gap along the complementary undamaged DNA strand and “stitch” the built-in nucleotides. The most remarkable thing about the DNA repair process is that it, as it were, repeats in miniature those main links of the regenerative process that we are accustomed to observing when it unfolds at the tissue level - damage, enzymatic breakdown of dead tissue and cleansing of the damaged area within healthy tissues, filling the resulting defect with newly formed tissue of the same type (complete regeneration) or connective tissue (incomplete regeneration). This indicates that with all the seemingly infinite variety of processes unfolding in the body, each of them, in principle, proceeds according to some universal standard scheme common to all levels of organization.
Regeneration, occurring at the molecular and ultrastructural levels, is limited to cells, and therefore it is called intracellular. Structural support for the body’s adaptation to everyday environmental influences is provided by corresponding fluctuations in intensity physiological regeneration , which in case of illness sharply intensifies and takes on the character reparative. Both physiological and reparative regeneration in some organs is ensured by all its forms - cellular (mitosis, amitosis) and intracellular. In organs and systems such as the central nervous system and heart (myocardium), where cell reproduction is absent, the structural basis for the normalization of their function is exclusively intracellular regeneration. Thus, the latter is a universal form of regeneration, characteristic of all organs without exception.
Reparative regeneration It can be complete, incomplete and intracellular.
Cellular form regeneration is inherent in the following organs and tissues (bone, hematopoietic, loose connective tissue, endothelium, mesothelium, mucous membranes of the gastrointestinal tract, genitourinary system, respiratory organs, skin, lymphoid tissue),
To organs and tissues where it predominates intracellular form of regeneration, include the myocardium and nerve cells.
In some organs, cellular and intracellular forms of regeneration are observed - liver, kidneys, lungs, smooth muscles, endocrine glands, pancreas, autonomic nervous system.
The morphogenesis of the reparative process consists of two phases - proliferation and differentiation. The first phase involves the reproduction of young undifferentiated cells (cambial, stem or progenitor cells). By multiplying and then differentiating, they make up for the loss of highly differentiated cells. There is another point of view about the sources of regeneration. It is assumed that the source of regeneration can be highly differentiated cells of an organ, which, under conditions of a pathological process, can be rebuilt, lose some of their specific organelles and at the same time acquire the ability for mitotic division with subsequent proliferation and differentiation. The outcomes of the regeneration process may vary. In some cases, reparative regeneration ends with the formation of a part identical to the dead one - then they speak of complete regeneration or restitution. In others, incomplete regeneration (substitution) occurs. In the area of damage, tissue that is not specific to this organ is formed, but connective tissue, which is subsequently subject to scarring. In this case, the remaining structures compensatory increase in their mass, i.e. hypertrophy. Regenerative hypertrophy occurs, which is an expression of the essence of incomplete regeneration. Regenerative hypertrophy can be carried out in two ways - hyperplasia of cells (liver, kidneys, pancreas, lungs, spleen, etc.) and ultrastructures (hypertrophy of cells - myocardium and neurons of the brain). Mainly those tissues that are characterized by cellular regeneration are completely regenerated; striated muscles, myocardium, and large vessels are incompletely regenerated. Regeneration.hypertrophy is observed in the liver, lungs, kidneys, endocrine glands, and the ANS.
Pathological regeneration– a distortion of the regeneration process towards hyporegeneration or hyperregeneration, in fact this is an incorrectly proceeding reparative regeneration. Examples of such regeneration and their reasons are:
1. The tissues have not lost their regenerative ability, but due to physical and biochemical conditions, regeneration takes on an excessive nature, resulting in tumor-like growths and leading to dysfunction (intensive growth of granulation tissue in wounds /excessive granulations/, keloid scars after burns, amputation neuromas).
2. Loss of habitual, adequate rates of regeneration by tissues (for example, in case of exhaustion, vitamin deficiencies, diabetes) - long-term non-healing wounds, false joints, epithelial metaplasia - in the focus of chronic inflammation).
3. Regeneration is of a qualitatively new nature in relation to the emerging tissues, which is associated with the functional inferiority of the regenerate (for example, the formation of false lobules in cirrhosis of the liver), and sometimes its transition into a new qualitative process - a tumor.
Regeneration carried out under the influence of various regulatory mechanisms:
1) humoral (hormones, poetic factors, growth factor, kelons)
2) immunological (the fact of transfer of “regenerative information” by lymphocytes has been established, stimulating the proliferative activity of cells of various internal organs
3) nervous and
4) functional (dosed functional load).
The effectiveness of regeneration processes is largely determined by the conditions in which it occurs. The general condition of the body is of great importance in this regard. Exhaustion, hypovitaminosis, impaired innervation, etc. have a significant impact on the course of reparative regeneration, inhibiting it and turning it pathological. The degree of functional load has a significant influence, the correct dosage of which promotes regeneration (restoration of bone tissue during fractures). The rate of reparative regeneration is to a certain extent determined by age, constitution, metabolism, and nutrition. Local factors are also important - the state of innervation, blood and lymph circulation, the nature of the pathological process, and the proliferative activity of cells.
Wound healing occurs according to the laws of reparative regeneration. Depending on the depth of the defect, the type of tissue and treatment methods, 4 types of wound healing are distinguished.
1. Direct closure of epithelial defect, in which there is a creep of epithelial cells onto the surface of the defect from the area of the edges of the damage.
2. Healing under the scab occurs in small defects, on the surface of which a crust (scab) forms, under which epithelial cells grow within 3-5 days, after which the crust disappears.
3. Primary tension.
4. Secondary tension.
Healing by primary intention occurs in the area of treated and sutured skin wounds or minor defects of organs and tissues, in which, due to mild tissue trauma and low microbial invasion, dystrophic and necrobotic changes in cells and fibers are minimal even at the ultrastructural level. The primary reaction of mast cells and microcirculation vessels is relatively weak, therefore exudation is moderate and serous in nature, the neutrophil and macrophage stages of the inflammatory cellular reaction are weakened due to the low concentration of mediators that determine the chemotaxis of these cells. This leads to rapid cleansing of the wound and transition to the proliferative phase - the appearance of fibroblasts, new formation of capillaries, then argyrophilic and collagen fibers. Granulation tissue, which is weakly expressed at initial intention, quickly matures (10-15 days). The surface of the defect is epithelialized and a delicate scar is formed at the site of the wound.
Healing by secondary intention occurs with large and deep, open defects, with active microbial invasion through suppuration. At the border with dead tissue, demarcation purulent inflammation develops. Within 5-6 days, necrotic masses are rejected (secondary wound cleansing) and granulation tissue begins to form at the edges of the wound. Granulation tissue, which gradually fills the wound defect, has pronounced signs of inflammation and a complex six-layer structure, described by N.N. Anichkov:
1. superficial leukocyte-necrotic layer
2. superficial layer of vascular loops
3. layer of vertical vessels
4. maturing layer
5. layer of horizontal fibroblasts
6. fibrous layer.
Regeneration lost organs in animals is a mystery that has troubled scientists since ancient times. Until recently, it was believed that only lower species of living beings were endowed with this magnificent property: a lizard grows back a severed tail, some worms can be cut into small pieces, and each one will grow into a whole worm - there are many examples.
But the evolution of the living world went from lower organisms to increasingly more highly organized ones, so why did this property disappear at some stage? And was it lost?
The Lernaean Hydra, the Gorgon Medusa or our three-headed Serpent Gorynych, whose “self-repairing” heads Ivan tirelessly chopped off, are characters, although mythical, but clearly in a “family relationship” with very real creatures.
These include, for example, newts, a type of tailed amphibian that is rightfully considered one of the most ancient animals on Earth. Their amazing feature is the ability to regenerate - to regrow damaged or lost tails, paws, and jaws.
Moreover, their damaged heart, eye tissue, and spinal cord are restored. For this reason, they are indispensable for laboratory research, and newts are sent into space no less often than dogs and monkeys. Many other creatures have these same properties.
Thus, black and white zebrafish, only 2-3 cm long, tend to regenerate parts of their fins, eyes, and even restore the cells of their own heart, cut out by surgeons during regeneration experiments. This can be said about other types of fish.
Classic examples of regeneration are lizards and tadpoles that regenerate a lost tail; crayfish and crabs growing back their lost claws; snails that can grow new “horns” with eyes; salamanders, which naturally replace an amputated leg; starfish regenerating their severed rays.
By the way, from such a severed ray, like from a cutting, a new animal can develop. But the champion of regeneration was the flatworm, or planaria. If it is cut in half, then the missing head grows on one half of the body, and the tail grows on the other, that is, two completely independent viable individuals are formed.
And perhaps the appearance of a completely unusual, two-headed and two-tailed planaria. This will happen if longitudinal cuts are made at the front and rear ends and do not allow them to grow together. Even 1/280 of the body of this worm will make a new animal!
People watched our smaller brothers for a long time and, to be honest, secretly envied them. And scientists moved from fruitless observations to analysis and tried to identify the laws of this “self-healing” and “self-healing” of animals.
The first to try to bring scientific clarity to this phenomenon was the French naturalist Rene Antoine Reaumur. It was he who introduced into science the term “regeneration” - the restoration of a lost part of the body with its structure (from the Latin ge - “again” and generatio - “emergence”) - and conducted a series of experiments. His work on leg regeneration in cancer was published in 1712. Alas, her colleagues did not pay attention to her, and Reaumur abandoned this research.
Only 28 years later, the Swiss naturalist Abraham Tremblay continued his experiments on regeneration. The creature on which he experimented did not even have its own name at that time. Moreover, scientists did not yet know whether it was an animal or a plant. A hollow stalk with tentacles, with its rear end attached to the glass of an aquarium or to aquatic plants, turned out to be a predator, and a very surprising one at that.
In the researcher's experiments, individual fragments of the small predator's body turned into independent individuals - a phenomenon known until then only in the plant world. And the animal continued to amaze the natural scientist: in place of the longitudinal cuts on the front end of the body made by the scientist, it grew new tentacles, turning into a “many-headed monster,” a miniature mythical hydra, which, according to the ancient Greeks, Hercules fought with.
It is not surprising that the laboratory animal received the same name. But the hydra under study had even more wonderful features than its Lernaean namesake. She grew to a whole even from 1/200 of her one-centimeter body!
Reality surpassed fairy tales! But the facts that are known to every schoolchild today, published in 1743 in the Proceedings of the Royal Society of London, seemed implausible to the scientific world. And then Tremblay was supported by the already authoritative Reaumur, confirming the authenticity of his research.
The “scandalous” topic immediately attracted the attention of many scientists. And soon the list of animals with regenerative abilities turned out to be quite impressive. True, for a long time it was believed that only lower living organisms possess a self-renewal mechanism. Then scientists discovered that birds were able to grow beaks, and young mice and rats were able to grow tails.
Even mammals and humans have tissues with great capabilities in this area - many animals regularly change their fur, the scales of the human epidermis are renewed, cropped hair and shaved beards grow back.
Man is not only an extremely inquisitive creature, but also passionately desires to use any knowledge for his own benefit. Therefore, it is quite understandable that at a certain stage of research into the mysteries of regeneration, the question arose: why does this happen and is it possible to induce regeneration artificially? And why did higher mammals almost lose this ability?
Firstly, experts noted that regeneration is closely related to the age of the animal. The younger it is, the easier and faster the damage is corrected. A tadpole's missing tail easily grows back, but the loss of an old frog's leg makes it disabled.
Scientists studied the physiological differences, and the method used by amphibians for “self-repair” became clear: it turned out that in the early stages of development, the cells of the future creature are immature, and the direction of their development may well change. For example, experiments on frog embryos have shown that when the embryo has only a few hundred cells, part of the tissue destined to become skin can be cut out of it and placed in the brain area. And this tissue... will become part of the brain!
If a similar operation is performed on a more mature embryo, then skin still develops from skin cells - right in the middle of the brain. Therefore, scientists concluded that the fate of these cells is already predetermined. And if for the cells of most higher organisms there is no way back, then the cells of amphibians are able to turn back time and return to the moment when their purpose could have changed.
What is this amazing substance that allows amphibians to “self-heal”? Scientists have discovered that if a newt or salamander loses a leg, then the bone, skin and blood cells in the damaged area of the body lose their distinctive features.
All secondarily “newborn” cells, which are called blastema, begin to rapidly divide. And in accordance with the needs of the body, they become cells of bones, skin, blood... to eventually become a new paw. And if at the moment of “self-repair” you add tretinoinic acid (vitamin A acid), then this boosts the regenerative abilities of frogs so much that they grow three legs instead of the one lost.
For a long time it remained a mystery why the regeneration program was suppressed in warm-blooded animals. There may be several explanations. The first comes down to the fact that warm-blooded animals have slightly different priorities for survival than cold-blooded animals. Scarring of wounds became more important than total regeneration, since it reduced the chances of fatal bleeding when wounded and the introduction of a deadly infection.
But there may be another explanation, much darker - cancer, that is, the rapid restoration of a large area of damaged tissue implies the emergence of identical rapidly dividing cells in a certain place. This is exactly what is observed during the emergence and growth of a malignant tumor. Therefore, scientists believe that it has become vital for the body to destroy rapidly dividing cells, and therefore, the ability to quickly regenerate has been suppressed.
Doctor of Biological Sciences Pyotr Garyaev, Academician of the Russian Academy of Medical and Technical Sciences, states: “It (regeneration) did not disappear, it’s just that higher animals, including humans, turned out to be more protected from external influences and complete regeneration became less necessary.”
To some extent, it has been preserved: wounds and cuts heal, torn skin is restored, hair grows, and the liver partially regenerates. But our severed arm no longer grows back, just as our internal organs do not grow back to replace those that have ceased to function. Nature simply forgot how to do this. Perhaps I need to remind her of this.
As always, His Majesty Chance helped. Immunologist Helen Heber-Katz of Philadelphia once gave her laboratory assistant a routine task: piercing the ears of laboratory mice to attach tags to them. A couple of weeks later, Heber-Katz came to the mice with ready-made tags, but... did not find holes in the ears.
We did it again and got the same result: no hint of a healed wound. The mice's bodies regenerated tissue and cartilage, filling in unnecessary holes. Herber-Katz drew the only correct conclusion from this: in the damaged areas of the ears there is a blastema - the same unspecialized cells as in amphibians.
But mice are mammals, they should not have such abilities. Experiments on the unfortunate rodents continued. Scientists cut off pieces of mice's tails and... got 75 percent regeneration! True, no one even tried to cut off the “patients’” paws for an obvious reason: without cauterization, the mouse would simply die from massive blood loss long before regeneration of the lost limb began (if at all). And cauterization eliminates the appearance of blastema. So it was not possible to find out a complete list of the regenerative abilities of mice. However, we have already learned a lot.
True, there was one “but”. These were not ordinary house mice, but special pets with a damaged immune system. Heber-Katz made the first conclusion from her experiments: regeneration is inherent only in animals with destroyed T-cells - cells of the immune system.
Here's the main problem: amphibians don't have it. This means that the answer to this phenomenon lies precisely in the immune system. Conclusion two: mammals have the same genes necessary for tissue regeneration as amphibians, but T cells do not allow these genes to work.
Conclusion three: organisms originally had two ways of healing from wounds - the immune system and regeneration. But over the course of evolution, the two systems became incompatible with each other - and mammals chose T cells because they were more important, since they were the body's main weapon against tumors.
What is the use of being able to regrow a lost arm if at the same time cancer cells are rapidly developing in the body? It turns out that the immune system, while protecting us from infections and cancer, simultaneously suppresses our ability to “self-repair.”
But is it really impossible to think of anything, because you really want not just rejuvenation, but restoration of the life-supporting functions of the body? And scientists have found, if not a panacea for all ills, then an opportunity to become a little closer to nature, however, thanks not to the blastema, but to stem cells. It turned out that humans have a different principle of regeneration.
For a long time it was known that only two types of our cells can regenerate - blood cells and liver cells. When the embryo of any mammal develops, some cells remain aside from the process of specialization.
These are stem cells. They have the ability to replenish blood or dying liver cells. Bone marrow also contains stem cells that can become muscle tissue, fat, bone or cartilage, depending on what nutrients they are given in the laboratory.
Now scientists had to test experimentally whether there was a chance to “launch” the “instructions” written in the DNA of each of our cells for growing new organs. Experts were convinced that you just need to force the body to “turn on” its ability, and then the process will take care of itself. True, the ability to grow limbs immediately runs into a temporary problem.
What a tiny body can easily do is beyond the power of an adult: the volumes and dimensions are much larger. We can't do like newts: form a very small limb and then grow it. For this, amphibians need only a couple of months; for a person to grow a new leg to normal size, according to the calculations of the English scientist Jeremy Brox, it takes at least 18 years...
But scientists have found a lot of work for stem cells. However, first it is necessary to say how and where they are obtained from. Scientists know that the largest number of stem cells is located in the bone marrow of the pelvis, but in any adult they have already lost their original properties. The most promising resource is considered to be stem cells obtained from umbilical cord blood.
But after birth, researchers can only collect 50 to 120 ml of such blood. From every 1 ml, 1 million cells are released, but only 1% of them are progenitor cells. This personal reserve of the body’s recovery reserve is extremely small and therefore priceless. Therefore, stem cells are obtained from the brain (or other tissues) of embryos - abortive material, no matter how sad it is to talk about it.
They can be isolated, placed in tissue culture, where reproduction begins. These cells can live in culture for more than a year and can be used for any patient. Stem cells can be isolated from umbilical cord blood and from the brain of adults (for example, during neurosurgery).
Or it can be isolated from the brains of recently deceased people, since these cells are resistant (compared to other cells of the nervous tissue); they are preserved when the neurons have already degenerated. Stem cells extracted from other organs, such as the nasopharynx, are not as versatile in their use.
Needless to say, this direction is fantastically promising, but has not yet been fully explored. In medicine, it is necessary to measure seven times, and then recheck for ten years to make sure that the panacea does not lead to any disaster, for example, an immune shift. Oncologists also did not say their strong “yes”. But nevertheless, there have already been successes, although only at the level of laboratory developments and experiments on higher animals.
Let's take dentistry as an example. Japanese scientists have developed a treatment system based on genes that are responsible for the growth of fibroblasts - the very tissues that grow around teeth and hold them. They tested their method on a dog that had previously developed a severe form of periodontal disease.
When all the teeth fell out, the affected areas were treated with a substance that included these same genes and agar-agar, an acidic mixture that provides a nutrient medium for cell reproduction. Six weeks later, the dog's fangs erupted.
The same effect was observed in a monkey with teeth cut down to the base. According to scientists, their method is much cheaper than prosthetics and for the first time allows a huge number of people to literally return their teeth. Especially when you consider that after 40 years of age, a tendency to periodontal disease occurs in 80% of the world's population.
In another series of experiments, the tooth chamber was filled with dentinal filings (playing the role of an inductor) with gingival connective tissue (amphodont) as a reacting material. And the amphodont also turned into dentin. In the near future, English dentists hope to move from successful experiments on mice to further laboratory research. Conservative estimates suggest that stem implants will cost the same as conventional prosthetics in England - between £1,500 and £2,000.
Research has shown that people with kidney failure only need to have 10% of their kidney cells revived to stop being dependent on a dialysis machine.
And research in this direction has been ongoing for many years. How important it is - not to sew it on, but to grow it again, not to sit on pills, but to restore healthy function using the hidden capabilities of the body.
In particular, a way has been found to grow new pancreatic beta cells that produce insulin, which promises millions of diabetics relief from daily injections. And experiments on the possibility of using stem cells in the fight against diabetes are already in the completion phase.
Work is also underway to create products that include regeneration. Ontogeny has developed a growth factor called OP1, which will soon be approved for sale in Europe, the US and Australia. It stimulates the growth of new bone tissue. OP1 will help in the treatment of complex fractures, when the two parts of the broken bone are very misaligned with each other and therefore cannot heal.
Often in such cases the limb is amputated. But OP1 stimulates bone tissue so that it begins to grow and fill the gap between the parts of the broken bone. At the Russian Institute of Traumatology and Orthopedics, researchers obtain stem cells from bone marrow. After 4-6 weeks of propagation in culture, they are transplanted into the joint, where they reconstruct the cartilaginous surfaces.
And a few years ago, a group of English geneticists made a sensational announcement: they were starting work on heart cloning. If the experiment is successful, there will be no need for transplants, which could lead to tissue rejection. But it is unlikely that wave genetics will be limited to the regeneration of only internal organs, and scientists hope that they will learn to “grow” limbs for patients.
Stem cells also have great prospects in the field of gynecology. Unfortunately, many young women today are doomed to infertility: their ovaries have stopped producing eggs.
This often means that the pool of cells from which follicles arise has been exhausted. Therefore, it is necessary to look for mechanisms that replenish them. The first encouraging results in this area have appeared recently.
Scientists are already seeing how to save people who have been given a terrible diagnosis - cirrhosis of the liver. They believe that at some stages of the development of the disease, transplantation of an entire organ can be replaced by the introduction of only stem cells (through the arterial bed, direct punctures, direct cell transplantations into liver tissue). Specialists from the Center for Surgery of the Russian Academy of Medical Sciences have begun a pilot study, and the first results are encouraging.
Ukrainian scientists are conducting very interesting preliminary developments in the field of cardiovascular diseases. Already today they have accumulated experimental evidence that the introduction of stem cells to patients with myocardial infarction or severe ischemia is a promising method of treatment.
The first clinical experiments with stem cell transplantation, which began at the University of Pittsburgh in the USA, also yielded good results in severely ill patients who had suffered an ischemic or hemorrhagic stroke. After cell therapy, their neurological rehabilitation is clearly noticeable.
Unfortunately, the frightening statistics of the number of children with intrauterine brain damage, including cerebral palsy, are very well known. It has already been proven that if such children begin stem cell transplantation (or therapy aimed at stimulating them, i.e., localizing their own, endogenous cells in the affected area), then after the first year of life it is often observed that even with preservation of anatomical Children with brain defects have minimal neurological symptoms.
Effectively developed stem cell transplantation technologies can completely change our lives. But this is the future, and today this field of knowledge does not even have its own name, only options: “cell therapy”, “stem cell transplantation”, “regeneration medicine”, even “tissue engineering” and “organ engineering”.
But it is already possible to list all the possibilities of this new direction. It is not without reason that they say that the 21st century will pass under the sign of biology, and perhaps the experience of regeneration, preserved over millions of years by amphibians and protozoa, will help humanity.
Regeneration (from the Latin regeneratio - rebirth) is a process of renewal of all functioning structures of the body (biomolecules, cellular organelles, cells, tissues, organs and the whole organism) and is a manifestation of the most important attribute of life - self-renewal. Thus, physiological regeneration at the cellular and tissue level is the renewal of the epidermis, hair, nails, cornea, epithelium of the intestinal mucosa, peripheral blood cells, etc. According to the isotope method, the composition of the atoms of the human body is updated by 98% during the year. In this case, the cells of the stomach mucosa are renewed in 5 days, fat cells - in 3 weeks, skin cells - in 5 weeks, skeletal cells - in 3 months.
Regeneration in the broad sense of the word is the normal renewal of organs and tissues, the restoration of what has been lost, the elimination of damage, and, finally, reconstruction (reconstruction of an organ).
The body has two main strategies for tissue replacement and self-renewal (regeneration). The first way is that differentiated cells are replaced as a result of their formation of new ones from regional stem cells. An example of this category is hematopoietic stem cells. The second way is that tissue regeneration occurs due to differentiated cells, but retaining the ability to divide: for example, hepatocytes, skeletal muscle and endothelial cells.
Regeneration phases: proliferation (mitosis, increase in the number of undifferentiated cells), differentiation (structural and functional specialization of cells) and morphogenesis.
Types and forms of regeneration
1. Cellular regeneration is cell renewal as a result of mitosis of undifferentiated or poorly differentiated cells.
For the normal course of regeneration processes, a decisive role is played not only by stem cells, but also by other cellular sources, the specific activation of which is carried out by biologically active substances (hormones, prostaglandins, poetins, specific growth factors):
- activation of reserve cells that have stopped at an early stage of their differentiation and do not participate in the development process until they receive a stimulus for regeneration
Temporary dedifferentiation of cells in response to a regenerative stimulus, when differentiated cells lose signs of specialization and then differentiate again into the same cell type
Metaplasia is a transformation into cells of a different type: for example, a chondrocyte is transformed into a myocyte or vice versa (an organ preparation as an adequate determinant stimulus for physiological cell metaplasia).
2. Intracellular regeneration- renewal of membranes, preserved organelles or an increase in their number (hyperplasia) and size (hypertrophy).
3. Biochemical regeneration- updating the biomolecular composition of the cell, its organelles, nucleus, cytoplasm (for example, peptides, growth factors, collagen, hormones, etc.). The intracellular form of regeneration is universal, since it is characteristic of all organs and tissues.
Reparative regeneration(from Latin reparatio - restoration) occurs after damage to a tissue or organ (for example, mechanical trauma, surgery, the action of poisons, burns, frostbite, radiation exposure, etc.). Reparative regeneration is based on the same mechanisms that are characteristic of physiological regeneration.
The ability to repair internal organs is very high: the liver, ovary, intestinal mucosa, etc. An example is the liver, in which the source of regeneration is practically inexhaustible, evidence of which is the well-known experimental data obtained on animals: with 12-fold removal of a third of the liver over the course of a year, by the end of the year in rats, under the influence of organ preparations, the liver restored its normal size.
Reparative regeneration of tissues such as muscle and skeletal has certain characteristics. For muscle repair, it is important to preserve small stumps at both ends, and for bone regeneration, periosteum is necessary. Reparation inducers are biologically active substances released when tissue is damaged. In addition, individual fragments of the same damaged tissue can be inducers: complete replacement of the skull bone defect can be achieved after the introduction of bone filings into it.
Reparative regeneration can occur in two forms.
1. Complete regeneration - the area of necrosis is filled with tissue identical to the dead one, and the site of damage disappears completely. This form is typical for tissues in which regeneration occurs predominantly in cellular form. Complete regeneration includes the restoration of intracellular structures during cell degeneration (for example, fatty degeneration of hepatocytes in people who abuse alcohol).
2. Incomplete regeneration – the area of necrosis is replaced by connective tissue, and normalization of organ function occurs due to hyperplasia of the remaining surrounding cells (myocardial infarction). This method occurs in organs with predominantly intracellular regeneration.
Prospects for scientific research on regeneration. Currently, organopreparations are being actively studied - extracts of the contents of a living cell with all its important cellular macromolecules (proteins, bioregulatory substances, growth and differentiation factors). Each tissue has a certain biochemical specificity of its cellular contents. Thanks to this, a large number of organ preparations are manufactured that are targeted at specific tissues and organs.
In general, the direct influence of organopreparations, as standards of cell biochemistry, consists primarily in eliminating the cellular imbalance of bioregulators of regeneration processes, maintaining the balance of optimal concentrations of biomolecules and preserving chemical homeostasis, which is disturbed not only under any pathology, but also during functional changes. This leads to restoration of mitotic activity, cell differentiation and regenerative potential of the tissue. Organic preparations provide the quality of the most important characteristic of the process of physiological regeneration - they contribute to the appearance in the process of division and differentiation of healthy and functionally active cells that are resistant to environmental toxins, metabolites and other influences. Such cells form a specific microenvironment, characteristic of a given type of healthy tissue, which has an inhibitory effect on existing “plus tissues” and prevents the appearance of malignant cells.
So, the influence of organopreparations on the processes of physiological regeneration is that, on the one hand, they stimulate immature developing cells of homologous tissue (regional stem cells, etc.) to develop normally into mature forms, i.e. stimulate the mitotic activity of normal tissues and cell differentiation, and on the other hand, normalize cellular metabolism in homologous tissues. As a result, physiological regeneration occurs in homologous tissue with the formation of normal cell populations with optimal metabolism, and this entire process is physiological in nature. Thanks to this, when an organ is damaged (for example, skin or gastric mucosa), organ preparations provide ideal reparation - healing without a scar.
It must be emphasized that the restoration of mitotic activity and cell differentiation under the influence of organ preparations is key in correcting defects and anomalies in the development of organs in children.
In conditions of pathology or accelerated aging, physiological regeneration processes also take place, but they do not have the same quality - young cells appear that are not resistant to circulating toxins, do not sufficiently perform their functions, and are not able to resist pathogens, which creates conditions for the preservation of the pathological process in the tissue or organ, for the development of premature aging. Hence, the expediency of using organopreparations as means that can most effectively restore the regenerative potential and biochemical homeostasis of tissue, organ and the whole organism and thus prevent the aging process is clear and obvious. And this is nothing more than revitalization.
Surprisingly, if the lizard's tail falls off, the missing part will re-form from the remaining part. In some cases, reparative regeneration is so perfect that the entire multicellular organism is restored from only a small fragment of tissue. Our body spontaneously sheds cells from the surface of the skin and replaces them with newly formed ones. This happens precisely because of regeneration.
Types of regeneration
Reparative regeneration is a natural ability of all living organisms. It is used to replace worn parts, renew damaged and lost fragments, or recreate the body from a small area during the post-embryonic life of the organism. Regeneration is a process that includes growth, morphogenesis and differentiation. Today, all types and types of reparative regeneration are actively used in medicine. This process occurs not only in humans, but also in animals. Regeneration is divided into two types:
- physiological;
- reparative.
There is a constant loss of many structures in our body due to wear and tear. The replacement of these cells is due to physiological regeneration. An example of such a process is the renewal of red blood cells. Worn out skin cells are constantly replaced by new ones.
Reparative regeneration is the process of restoring lost or damaged organs and body parts. In this type, tissues are formed by expanding adjacent fragments.
- Regeneration of limbs in a salamander.
- Restoring a lost lizard tail.
- Wound healing.
- Replacing damaged cells.
Types of reparative regeneration. Morphallaxis and epimorphosis
There are different types of reparative regeneration. In our article you can find more detailed information about them. Epimorphic regeneration involves the differentiation of adult structures to form an undifferentiated mass of cells. It is with this process that the recovery of a deleted fragment is associated. An example of epimorphosis is the regeneration of limbs in amphibians. In the morphallaxis type, regeneration occurs mainly due to the rearrangement of existing tissues and the restoration of boundaries. An example of such a process is the formation of a hydra from a small fragment of its body.
Reparative regeneration and its forms
Recovery occurs due to the spread of neighboring tissues, which fill with young cells with a defect. Subsequently, full-fledged mature fragments are formed from them. Such forms of reparative regeneration are called restoration.
There are two options for this process:
- The loss is compensated by fabric of a similar type.
- The defect is replaced with new tissue. A scar forms.
Bone tissue regeneration. New method
In the modern medical world, reparative bone tissue regeneration is a reality. This technique is most often used in bone graft surgery. It is worth noting that collecting enough material for such a procedure is incredibly difficult. Fortunately, a new surgical method for repairing damaged bones has emerged.
Thanks to biomimicry, researchers have developed a new method for restoring bone structure. Its main purpose is to use sea sponge corals as scaffolds or frames for bone tissue. Thanks to this, damaged fragments will be able to repair themselves. Corals are ideal for this type of surgery because they integrate easily into existing bones. Their structure also coincides in terms of porosity and composition.
The process of restoring bone tissue using corals
To restore using the new method, surgeons must prepare coral or sea sponges. They also need to select substances such as stromal or bone marrow, which are capable of becoming any other adamantoblast in the body. Reparative tissue regeneration is a rather labor-intensive process. During the operation, sponges and cells are inserted into a section of damaged bone.
Over time, the bone fragments either regenerate or the stem adamantoblasts expand the existing tissue. Once the bone fuses, the coral or becomes part of it. This is due to their similarity in structure and composition. Reparative regeneration and methods for its implementation are being studied by specialists from all over the world. It is thanks to this process that you can cope with some acquired deficiencies of the body.
Epithelial restoration
Methods of reparative regeneration play an important role in the life of any living organism. Transitional epithelium is a multilayered covering that is characteristic of urinary drainage organs such as the bladder and kidneys. They are most susceptible to sprains. It is in them that tight junctions are located between the cells, which prevent the penetration of fluid through the wall of the organ. The adamanthoblasts of the urinary drainage organs quickly wear out and weaken. Reparative regeneration of epithelium occurs due to the content of stem cells in organs. They retain the ability to divide throughout their entire life cycle. Over time, the update process deteriorates significantly. This is associated with numerous diseases that occur in many people with age.
Mechanisms of reparative regeneration of the skin. Their influence on the recovery of the body after burn injuries
It is known that burns are the most common injury among children and adults. Today the topic of such injuries is extremely popular. It is no secret that burn injuries can not only leave a scar on the body, but also cause surgical intervention. To date, there is no such procedure that would completely get rid of the resulting scar. This is due to the fact that the mechanisms of reparative regeneration are not fully understood.
There are three degrees of burn injuries. It is known that more than 4 million people suffer from skin damage caused by exposure to steam, hot water or a chemical. It's worth noting that scarred skin is not the same as the skin it replaces. It also differs in its functions. The newly formed tissue is weaker. Today, experts are actively studying the mechanisms of reparative regeneration. They believe that they will soon be able to completely rid patients of burn scars.
Level of reparative regeneration of bone tissue. Optimal conditions for the process
Reparative regeneration of bone tissue and its level are determined by the degree of damage in the fracture area. The more microcracks and injuries, the slower the formation of callus will occur. It is for this reason that experts prefer treatment methods that are not associated with causing additional damage. The most optimal conditions for reparative regeneration in bone fragments are immobility of the fragments and slow distraction. If they are absent, connective fibers are formed at the fracture site, which subsequently form
Pathological regeneration
Physical and reparative regeneration plays an important role in our lives. It is no secret that for some this process may be slowed down. What is this connected with? You can find out this and much more in our article.
Pathological regeneration is a violation of recovery processes. There are two types of such recovery - hyperregeneration and hyporegeneration. The first process of formation of new tissue is accelerated, and the second is slow. These two types are a violation of regeneration.
The first signs of pathological regeneration are the formation of long-term healing injuries. Such processes arise as a consequence of disruption of local conditions.
How to speed up the process of physiological and reparative regeneration
Physiological and reparative regeneration plays an important role in the life of every living creature. Examples of such a process are known to absolutely everyone. It is no secret that some patients have injuries that take a long time to heal. Any living organism must have a complete diet, which includes a variety of vitamins, microelements and nutrients. With a lack of nutrition, energy deficiency occurs and trophic processes are disrupted. As a rule, patients develop one or another pathology.
To speed up the regeneration process, it is necessary to first remove dead tissue and take into account other factors that may affect recovery. These include stress, infections, dentures, lack of vitamins, and much more.
To speed up the regeneration process, a specialist may prescribe a vitamin complex, anabolic agents and biogenic stimulants. In home medicine, sea buckthorn oil, carotoline, as well as juices, tinctures and decoctions of medicinal herbs are actively used.
Shilajit to speed up regeneration
Reparative regeneration includes complete or partial restoration of damaged tissues and organs. Does this process speed up the mummy? What it is?
It is known that mumiyo has been used for 3 thousand years. This is a biologically active substance that flows from the crevices of the rocks of the southern mountains. Its deposits are found in more than 10 countries around the world. Mumiyo is a dark brown sticky mass. The substance dissolves well in water. Depending on the place of collection, the composition of the mumiyo may differ. Nevertheless, absolutely each of them contains a vitamin complex, a number of minerals, essential oils and bee venom. All these components contribute to the rapid healing of wounds and injuries. They also improve the body's response to adverse conditions. Unfortunately, there is no drug based on mumiyo to accelerate regeneration, since the substance is difficult to process.
Regeneration in animals. general information
As we said earlier, the regeneration process occurs in absolutely any living organism, including animals. It is worth noting that the higher it is organized, the worse the recovery takes place in its body. In animals, reparative regeneration is the process of reproducing lost or damaged organs and tissues. The simplest organisms restore their body only in the presence of a nucleus. If it is missing, then the lost parts are not reproduced.
There is an opinion that siskins can restore their limbs. However, this information has not been confirmed. Mammals and birds are known to repair only tissue. However, the process has not been fully studied.
The easiest way for animals to recover is nervous and muscle tissue. In most cases, new fragments are formed from the remains of old ones. A significant increase in regenerating organs has been observed in amphibians. A similar thing occurs in lizards. For example, instead of one tail, two grow.
After conducting a number of studies, scientists have proven that if a lizard’s tail is cut off obliquely and in doing so touches not one, but two or more spines, then the reptile will grow 2-3 tails. There are also cases when an animal may recover an organ not where it was previously located. Surprisingly, through regeneration, an organ can also be recreated that was not previously in the body of a particular creature. This process is called heteromorphosis. All methods of reparative regeneration are extremely important not only for mammals, but also for birds, insects, and unicellular organisms.
Let's sum it up
Each of us knows that lizards can easily completely restore their tail. Not everyone knows why this happens. Physiological and reparative regeneration plays an important role in everyone's life. To restore it, you can use both medications and home methods. Mumiyo is considered one of the best remedies. It not only speeds up the regeneration process, but improves the overall background of the body. Be healthy!
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