The regeneration of lost organs in animals is a mystery that has worried scientists since ancient times. Until recently, it was believed that only the lowest species of living creatures are endowed with this magnificent property: a lizard grows a severed tail, some worms can be cut into small pieces, and each will grow into a whole worm - there are many examples.
But after all, the evolution of the living world went from lower organisms to more and more highly organized ones, so why did this property disappear at some stage? And was it lost?
The Lernaean hydra, Medusa the Gorgon or our three-headed Serpent Gorynych, whose “self-healing” heads were tirelessly chopped off by Ivan Tsarevich, are mythical characters, but they are clearly in “kinship” with very real creatures.
These, for example, include newts - a species of tailed amphibians, which are 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, jaws.
Moreover, the damaged heart, eye tissues and spinal cord are also 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 the same properties.
So, zebrafish rerio black and white, only 2-3 cm long, tend to regenerate parts of the fins, eyes and even restore the cells of their own heart, cut out by surgeons during experiments on regeneration. The same can be said for other types of fish.
The classic examples of regeneration are lizards and tadpoles rebuilding a lost tail; crayfish and crabs growing lost claws; snails capable of growing new "horns" with eyes; salamanders, which naturally replace the amputated paw; sea stars regenerating their severed rays.
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By the way, a new animal can develop from a ray that has been torn off, like a cutting. But the champion of regeneration was the flatworm, or planaria. If you cut it in half, then the missing head grows on one half of the body, and the tail on the other, that is, two completely independent viable individuals are formed.
And the appearance of a completely extraordinary, two-headed and two-tailed planaria is possible. 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 part of this worm will make a new animal!
For a long time people watched our smaller brothers and, to be honest, secretly envied. And scientists moved from fruitless observation to analysis and tried to reveal 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 Latin ge - "again" and generatio - "emergence") - and conducted a series of experiments. His work on leg regeneration in cancer was published in 1712. Alas, colleagues did not pay attention to her, and Reaumur abandoned these studies.
Only 28 years later, the Swiss naturalist Abraham Tremblay continued his experiments on regeneration. The creature on which he experimented did not even have a name at that time. Moreover, scientists did not yet know whether it was an animal or a plant. The hollow stem with tentacles, with its rear end attached to the glass of the aquarium or to aquatic plants, turned out to be a predator, and also quite amazing.
In the researcher's experiments, individual fragments of the body of a small predator turned into independent individuals - a phenomenon known until then only in the plant world. And the animal continued to amaze the natural scientist: at the site of the longitudinal cuts at the front end of the calf, 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.
Unsurprisingly, the laboratory animal received the same name. But the hydra being researched had even more wonderful features than its Lernaean namesake. She has grown to a whole even 1/200 of her one-centimeter body!
Reality exceeded fairy tales! But the facts that are known today to every schoolchild, published in 1743 in the "Proceedings of the Royal Society of London", seemed implausible to the scientific world. And then Tremblay supported by this time the already authoritative Reaumur, confirming the reliability of his research.
The "scandalous" topic immediately attracted the attention of many scientists. And soon the list of animals with the ability to regenerate turned out to be quite impressive. True, for a long time it was believed that only the lowest living organisms have a self-renewal mechanism. Scientists then discovered that birds can grow beaks, while young mice and rats can grow tails.
Even mammals and humans have tissues with great potential in this area - many animals regularly change their fur, the scales of the human epidermis are renewed, cut hair and shaved beards grow.
Man is a creature not only extremely inquisitive, but also passionately willing to use any knowledge for his own good. Therefore, it is quite understandable that at a certain stage in the study of the mysteries of regeneration, the question arose: why is this happening and is it possible to cause regeneration artificially? And why did higher mammals almost lose this ability?
First, the experts noted that regeneration is closely related to the age of the animal. The younger it is, the easier and faster the damage is repaired. In a tadpole, the missing tail easily grows back, but the loss of an old frog's leg makes it disabled.
Scientists investigated 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 a future creature are immature, and the direction of their development may well change. For example, experiments on frog embryos have shown that when an embryo has only a few hundred cells, a piece of tissue that is destined to become a skin can be cut out of it and placed in an area of the brain. And this tissue … will become part of the brain!
If such an operation is performed with a more mature embryo, then skin will still develop from skin cells - right in the middle of the brain. Therefore, scientists have 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 reverse time and return to the moment when their destination could change.
What is this amazing substance that allows amphibians to "self-repair"? Scientists have found that if a newt or salamander lose their paws, then in the damaged area of the body, the cells of bone, skin and blood lose their distinctive features.
All secondarily "newborn" cells, which are called blastema, begin to divide intensively. And in accordance with the needs of the body, they become cells of bones, skin, blood … to become at the end a new paw. And if at the moment of "self-repair" you connect tretinoic acid (acid of vitamin A), then this stimulates the regenerative abilities of frogs so much that they grow three legs instead of one lost.
For a long time it remained a mystery why the regeneration program was suppressed in warm-blooded animals. There can be several explanations. The first boils down to the fact that warm-blooded people have slightly different priorities for survival than cold-blooded ones. Scarring wounds became more important than total regeneration, as it reduced the chances of fatal bleeding when injured and the introduction of a deadly infection.
But there may be another explanation, much darker - cancer, that is, the rapid recovery of a vast area of damaged tissue implies the emergence of the same rapidly dividing cells in a certain place. This is what is observed during the onset 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 possibilities for rapid regeneration have been suppressed.
Doctor of Biological Sciences Petr Garyaev, Academician of the Russian Academy of Medical and Technical Sciences, says: "It (regeneration) has not disappeared, just higher animals, including humans, turned out to be more protected from external influences and complete regeneration was not so necessary."
To some extent, it has survived: wounds and cuts are healed, peeled skin is restored, hair grows, and the liver partially regenerates. But the severed hand no longer grows, just as the internal organs do not grow instead of those that have ceased to function. Nature simply forgot how to do it. Perhaps we should remind her of this.
As always, His Majesty Chance helped. Immunologist Helene Heber-Katz of Philadelphia once gave her laboratory assistant the usual task: to pierce the ears of laboratory mice to label them. A couple of weeks later, Heber-Katz came to the mice with ready-made labels, but … she did not find any holes in the ears.
We did it again and got the same result: no hint of a healed wound. The body of the mice regenerated tissue and cartilage by filling in the holes they did not need. Herber-Katz made the only correct conclusion from this: blastema is present in the damaged areas of the ears - the same non-specialized cells as in amphibians.
But mice are mammals, they shouldn't have that ability. Experiments on the unfortunate rodents continued. Scientists cut off pieces of tails for mice and … got 75 percent regeneration! True, no one even tried to cut off the "patients" paws for an obvious reason: without cauterization, the mouse will simply die of heavy blood loss long before the regeneration of the lost limb begins (if at all). And moxibustion excludes 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 damaged immune systems. The first conclusion from her experiments Heber-Katz made this: regeneration is inherent only in animals with destroyed T-cells - cells of the immune system.
Here's the main problem: amphibians do not have it. This means that the clue to this phenomenon is rooted in the immune system. The second conclusion: mammals have the same genes necessary for tissue regeneration as amphibians, but T cells do not allow these genes to work.
The third conclusion: organisms originally had two methods 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 are more important, since they are the body's main weapon against tumors.
What is the use of being able to regrow a lost hand if at the same time cancer cells grow rapidly in the body? It turns out that the immune system, while protecting us from infections and cancer, at the same time suppresses our ability to "self-repair".
But is it really impossible to come up with anything, because you really want not just rejuvenation, but the restoration of the life-supporting functions of the body? And scientists have found, if not a panacea for all ills, then the opportunity to become a little closer to nature, however, thanks not to 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 and liver cells. When the embryo of any mammal develops, some of the cells are left out of the specialization process.
These are stem cells. They have the ability to replenish blood or dying liver cells. Bone marrow also contains stem cells, which can become muscle, fat, bone, or cartilage, depending on what nutrients are given to them in the laboratory.
Now the scientists had to test empirically whether there is a chance to "launch" the "instruction" recorded 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 easily manages is beyond the power of an adult: volumes and sizes are much larger. We cannot do as newts do: 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 its normal size, according to the calculation 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 you need to say how and where they are obtained from. Scientists know that the largest number of stem cells is found in the bone marrow of the pelvis, but in any adult they have already lost their original properties. The most promising is the resource of stem cells obtained from umbilical cord blood.
But after giving birth, researchers can only collect 50 to 120 ml of such blood. From each 1 ml, 1 million cells are released, but only 1% of them are progenitor cells. This personal reserve of the body's restorative reserve is extremely small, and therefore invaluable. Therefore, stem cells are obtained from the brain (or other tissues) of embryos - an abortion material, no matter how sad it is to talk about it.
They can be isolated, placed in tissue culture, where reproduction will begin. These cells can live in culture for over 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).
And it can be isolated from the brain of recently deceased, 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 application.
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 a panacea does not entail any trouble, for example, an immune shift. Oncologists did not say their weighty "yes" either. But nevertheless, there are already successes, however, only at the level of laboratory developments, experiments on higher animals.
Take dentistry for example. Japanese scientists have developed a system of treatment based on genes that are responsible for the growth of fibroblasts - the very tissues that grow around the teeth and hold them. They tested their method on a dog that had previously developed severe periodontal disease.
When all the teeth fell out, the affected areas were treated with a substance that includes these same genes and agar-agar - an acid mixture that provides a nutrient medium for cell proliferation. Six weeks later, the dog's fangs erupted.
The same effect was observed in a monkey with teeth cut 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, 80% of the world's population is prone to periodontal disease.
In another series of experiments, the tooth chamber was filled with dentin sawdust (playing the role of an inductor) with the connective tissue of the gum (amphodont) as a reactive material. And the amphodont also turned into dentin. British dentists in the near future hope to move from successful experiments on mice to further laboratory research. By conservative estimates, "stem implants" will cost the same as conventional prosthetics in England - from £ 1,500 to £ 2,000.
Studies have shown that people who have kidney failure need to return only 10% of their kidney cells to life to stop relying on a dialysis machine.
And research in this direction has been going on for many years. How important it is - not to sew, but to grow again, not to sit on pills, but to restore a healthy function due to the hidden capabilities of the body.
In particular, a way has been found to grow new beta cells in the pancreas that produce insulin, promising millions of diabetics to get rid of daily injections. And experiments on the possibility of using stem cells in the fight against diabetes are already at the completion phase.
Work is also underway on the creation of funds that include regeneration. Ontogeny has developed a growth factor called OP1 that will soon be available for sale in Europe, the United States and Australia. It stimulates the growth of new bone tissue. OP1 will help in the treatment of complex fractures where the two pieces of the broken bone are too far out of alignment 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 fills the gap between the parts of the broken bone. At the Russian Institute of Traumatology and Orthopedics, researchers obtain stem cells from the bone marrow. After 4-6 weeks of reproduction in culture, they are transplanted into the joint, where they reconstruct the cartilaginous surfaces.
A few years ago, a group of British geneticists made a sensational statement: they begin work on cloning the heart. If the experiment is successful, there will be no need for tissue transplants. But it is unlikely that wave genetics will be limited to the regeneration of only internal organs, and scientists hope that they will learn how to "grow" limbs for patients.
In the field of gynecology, stem cells also hold great promise. 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 the follicles arise has been depleted. 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 people who have been diagnosed with cirrhosis of the liver can be saved. They believe that at some stages of the development of the disease, the transplantation of a whole organ can be replaced by the introduction of only stem cells (through the arterial bed, direct punctures, direct cell transplantation into liver tissue). Specialists of the Center for Surgery of the Russian Academy of Medical Sciences have begun a pilot study, and the first results are encouraging.
Very interesting preliminary developments are carried out by Ukrainian scientists in the field of cardiovascular diseases. Already today, they have accumulated experimental evidence that the introduction of stem cells into 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 United States, have yielded good results in critically ill patients who have suffered ischemic or hemorrhagic stroke. After cell therapy, neurological rehabilitation is clearly visible in them.
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 start stem cell transplantation (or therapy aimed at stimulating them, that is, localizing their own, endogenous, cells in the affected area), then after the first year of life, it is often observed that even while maintaining anatomical of brain defects, children have minimal neurological symptoms.
Effectively developed stem cell transplant technologies can completely change our lives. But this is the future, and today this area 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 enumerate all the possibilities of this new direction. It is not without reason that they say that the XXI century will be marked by biology, and, perhaps, the experience of regeneration, preserved for millions of years by amphibians and protozoa, will help humanity.
