What cells are responsible for regeneration. Physiological and reparative regeneration

Regeneration of organs and tissues, its types

Regeneration is the process of restoring lost or damaged tissues or organs.

There are two types of regeneration:

physiological

reparative

Physiological regeneration is manifested in the restoration of cells, tissues that die during the normal life of the body.

For example, the formed elements of the blood - erythrocytes, leukocytes - continuously die off, and the loss of these cells is replenished in the hematopoietic organs.

All the time, keratinized cells of the epidermis are torn off from the surface of the skin, and their restoration is continuously taking place.

Physiological regeneration includes hair change, replacement of milk teeth with permanent ones.

Reparative regeneration (Greek - repair) is manifested in the restoration of tissues or organs lost during damage.

Reparative regeneration underlies wound healing, bone fusion after fractures. Reparative regeneration occurs after burns.

There are the following methods of reparative regeneration:

1. Epithelialization

2. Epimorphosis

3. Morphallaxis

4. Endomorphosis (or hypertrophy)

epithelialization- healing of epithelial wounds. Regeneration comes from the wound surface.

The wound surface dries up with the formation of a crust. The epithelium along the edge of the wound thickens due to an increase in cell volume and expansion of intercellular spaces. A fibrin clot is formed. Epithelial cells with phagocytic activity migrate deep into the wound. There is an outbreak of mitosis. Epithelial cells from the sides of the wound grow under the lifeless necrotic tissue, separates the crust covering the wound.

Epimorphosis- a method of regeneration, which consists in the growth of a new organ from the amputated surface. Regeneration comes from the wound surface.

Epimorphic regeneration can be typical if the organ that has recovered after amputation does not differ from the intact one. Atypical, when the recovered organ differs in shape or structure from the normal one. An example of typical regeneration is the restoration of a limb in an axolotl after amputation. Axolotl (class amphibians) - ambystoma larva - object of experimental biology.

An example of atypical regeneration is limb regeneration in some lizard species. As a result, a tail-like appendage is formed instead of a limb.

Atypical regeneration includes heteromorphosis. For example, when the eye is removed, the jointed limb regenerates along with the nerve node at the base of the eye.

Morphallaxis- regeneration by restructuring the regenerating site - after amputation, the organ or organism regenerates, but of a smaller size.

An example is the regeneration of a hydra from a ring cut from the middle of its body, or the restoration of one tenth or twentieth.

Usually, regenerative processes occur in the area of ​​the wound surface.

But there are special forms of regeneration - these are endomorphosis (hypertrophy), which has two forms:

regenerative hypertrophy,

compensatory hypertrophy.

Regenerative hypertrophy - an increase in the size of the remainder of the organ without restoring the original shape (the size increases, but not the shape)

If a significant part of the liver or spleen is removed from a rat, the wound surface heals. Inside the remaining area, intensive cell proliferation begins. The volume of the liver increases, liver function returns to normal.

Compensatory hypertrophy is a change in one organ with a violation in another, related to the same organ system.

If one kidney is removed from a rabbit, then the second one receives an increased load. This causes it to grow, while its volume doubles.

Compensatory hypertrophy is not a reparative regeneration, because an undamaged organ grows. However, it is considered as a regenerative process of the system of excretory organs as a whole.

Regeneration cannot be considered as a local reaction. It is a process in which the organism as a whole participates. Nervous regulation is of particular importance. Regeneration occurs if the innervation is not disturbed. Some external factors slow down, others stimulate recovery processes.

Each organ and tissue has special conditions and patterns of regeneration. In a number of cases, regeneration proceeds successfully when special glass, plastic, and metal prostheses are used. Using prostheses, it was possible to obtain regeneration of the trachea, bronchi, large blood vessels. The prosthesis serves as a framework along which the endothelium of the vessel grows. There are many unresolved issues in the problem of regeneration. For example, the ear, the tongue does not regenerate in case of marginal damage, but in case of damage through the thickness of the organ, the restoration is successful.

Transplantation

Transplantation is the engraftment and development of transplanted tissues in a new place.

The organism from which the transplant material is taken is called the donor, and the one to which the transplant is performed is called the recipient. The transplanted tissue or organ is called a graft.

Distinguish:

1. Autotransplantation.

2. Homotransplantation (allotransplantation).

3. Heterotransplantation (xenotransplantation)

At autotransplantation the donor and recipient are the same organism, the graft is taken from one place and transplanted to another. This type of transplant is widely used in reconstructive surgery. For example, with extensive facial injuries, the skin of the arm or abdomen of the same patient is used. By autotransplantation, an artificial esophagus and rectum are created.

At allo- or homotransplantation donor and recipient are different individuals of the same species. In humans and higher animals, the success of homotransplantation depends on the antigenic compatibility of the tissues of the donor and recipient. If the donor tissues contain substances foreign to the recipient - antigens, then they cause the formation of immune antibodies in the recipient's body. The recipient's antibodies react with the antigens of the transplant and cause changes in the structure and function of the antigen and foreign tissue, rejection, which means that the tissues are immunologically incompatible. An example of allotransplantation in humans is a blood transfusion.

At heterotransplantation donor and recipient are animals of different species. In invertebrates, engraftment is possible. In higher animals, during transplantations of this kind, the graft, as a rule, resolves.

Currently, scientists and physicians are working on the problem of suppressing the immune reaction of rejection, overcoming immunological incompatibility. Immunological tolerance (tolerance) to foreign cells is of great importance.

Currently, there are several ways to prevent transplant rejection:

Selection of the most compatible donor

X-ray irradiation of the immune system of the bone marrow and lymphatic tissues. Irradiation inhibits the formation of lymphocytes and thus slows down the process of rejection.

The use of immunosuppressants, i.e. substances that not only suppressed the immune system, but selectively, specifically suppressed transplantation immunity, while maintaining the function of protection against infections. The search for specific immunosuppressants is currently underway. There are examples of the life of patients with transplanted kidneys, liver, pancreas.

People have always been amazed at the incredible properties of the animal body. Such properties of the body as the regeneration of organs, the restoration of lost parts of the body, the ability to change color and go without water and food for a long time, sharp eyesight, existence in incredibly difficult conditions, and so on. Compared with animals, it seems that they are not our "smaller brothers", but we are theirs.

But it turns out that the human body is not so primitive as it might seem to us at first glance.

Regeneration of the human body

Cells in our body are also updated. But how is the renewal of the cells of the human body? And if the cells are constantly being renewed, then why does old age come, and not eternal youth last?

Swedish neurologist Jonas Friesen found that every adult is on average fifteen and a half years old.

But if many parts of our body are constantly being updated, and as a result, they turn out to be much younger than their owner, then some questions arise:

• For example, why doesn't the skin remain smooth and pink all the time, like a baby's, if the top layer of the skin is always two weeks old?
• If the muscles are about 15 years old, then why is a 60-year-old woman not as flexible and mobile as a 15-year-old girl?

Friesen saw the answers to these questions in the DNA of mitochondria (this is part of every cell). She quickly accumulates various damage. That is why the skin ages over time: mutations in mitochondria lead to a deterioration in the quality of such an important component of the skin as collagen. According to many psychologists, aging occurs due to the mental programs that have been instilled in us since childhood.

Today we will consider the timing of the renewal of specific human organs and tissues:

Body Regeneration: Brain

Brain cells live with a person throughout his life. But if the cells were updated, the information that was embedded in them would go with them - our thoughts, emotions, memories, skills, experience.

A lifestyle such as: smoking, drugs, alcohol - to one degree or another destroys the brain, killing part of the cells.

And yet, in two areas of the brain, cells are updated:

• The olfactory bulb is responsible for the perception of smells.
• The hippocampus, which controls the ability to absorb new information in order to then transfer it to the "storage center", as well as the ability to navigate in space.

The fact that heart cells also have the ability to renew has become known only recently. According to researchers, this only happens once or twice in a lifetime, so it is extremely important to preserve this organ.

Body regeneration: Lungs

For each type of lung tissue, cell renewal occurs at a different rate. For example, the air sacs at the ends of the bronchi (alveoli) regenerate every 11 to 12 months. But the cells located on the surface of the lungs are updated every 14-21 days. This part of the respiratory organ takes on most of the harmful substances coming from the air we breathe.

Bad habits (primarily smoking), as well as a polluted atmosphere, slow down the renewal of the alveoli, destroy them and, in the worst case, can lead to emphysema.

Body regeneration: Liver

The liver is the champion of regeneration among the organs of the human body. Liver cells are renewed approximately every 150 days, that is, the liver is “born again” once every five months. It is able to recover completely, even if, as a result of the operation, a person has lost up to two-thirds of this organ.

The liver is the only organ in our body that has such a high regenerative function.

Of course, the detailed endurance of the liver is possible only with your help to this organ: the liver does not like fatty, spicy, fried and smoked foods. In addition, the work of the liver is greatly complicated by alcohol and most drugs.

And if you do not pay attention to this organ, it will cruelly take revenge on its owner with terrible diseases - cirrhosis or cancer. By the way, if you stop drinking alcohol for eight weeks, the liver can be completely cleansed.

Body regeneration: Intestine

The walls of the intestines are covered with tiny villi from the inside, which ensure the absorption of nutrients. But they are under the constant influence of gastric juice, which dissolves food, so they do not live long. Terms of their renewal - 3-5 days.

Body Regeneration: Skeleton

The bones of the skeleton are updated continuously, that is, at every moment in the same bone there are both old and new cells. It takes about ten years to completely renovate the skeleton.

This process slows down with age, as bones become thinner and more fragile.

Body regeneration: Hair

Hair grows an average of one centimeter per month, but hair can completely change in a few years, depending on the length. For women, this process takes up to six years, for men - up to three. Eyebrow and eyelash hairs grow back in six to eight weeks.

Body regeneration: Eyes

In such a very important and fragile organ as the eye, only corneal cells can be renewed. Its top layer is replaced every 7-10 days. If the cornea is damaged, the process occurs even faster - it is able to recover in a day.

Body regeneration: Language

10,000 receptors are located on the surface of the tongue. They are able to distinguish the tastes of food: sweet, sour, bitter, spicy, salty. The cells of the tongue have a rather short life cycle - ten days.

Smoking and oral infections weaken and inhibit this ability, as well as reduce the sensitivity of taste buds.

Body Regeneration: Skin and Nails

The surface layer of the skin is renewed every two to four weeks. But only if the skin is provided with proper care and it does not receive an excess of ultraviolet radiation.

Smoking negatively affects the skin - this bad habit accelerates skin aging for two to four years.

The most famous example of organ renewal is nails. They grow back 3-4 mm every month. But this is on the hands, on the legs the nails grow twice as slowly. The nail on the finger is completely renewed on average in six months, on the toe - in ten.

Moreover, on the little fingers, the nails grow much more slowly than the others, and the reason for this is still a mystery to physicians. The use of drugs slows down the recovery of cells throughout the body.

Now you know a little more about your body and its properties. It becomes obvious that a person is very complex and not fully understood. How much more do we have to find out?

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General information

Regeneration(from lat. regeneratio- revival) - restoration (reimbursement) of the structural elements of the tissue in exchange for the dead. In a biological sense, regeneration is adaptive process, developed in the course of evolution and inherent in all living things. In the life of an organism, each functional function requires the expenditure of a material substrate and its restoration. Therefore, during regeneration, self-reproduction of living matter, moreover, this self-reproduction of the living reflects principle of autoregulation And automation of vital functions(Davydovsky I.V., 1969).

The regenerative restoration of the structure can occur at different levels - molecular, subcellular, cellular, tissue and organ, however, it is always about the replacement of a structure that is capable of performing a specialized function. Regeneration is restoration of both structure and function. The value of the regenerative process is in the material support of homeostasis.

Restoration of structure and function can be carried out using cellular or intracellular hyperplastic processes. On this basis, cellular and intracellular forms of regeneration are distinguished (Sarkisov D.S., 1977). For cellular form regeneration is characterized by cell reproduction in the mitotic and amitotic way, for intracellular form, which can be organoid and intraorganoid, - an increase in the number (hyperplasia) and size (hypertrophy) of ultrastructures (nucleus, nucleoli, mitochondria, ribosomes, lamellar complex, etc.) and their components (see Fig. 5, 11, 15) . intracellular form regeneration is universal, since it is characteristic of all organs and tissues. However, the structural and functional specialization of organs and tissues in phylo- and ontogenesis "selected" for some the predominantly cellular form, for others - predominantly or exclusively intracellular, for the third - equally both forms of regeneration (Table 5). The predominance of one or another form of regeneration in certain organs and tissues is determined by their functional purpose, structural and functional specialization. The need to preserve the integrity of the integument of the body explains, for example, the predominance of the cellular form of regeneration of the epithelium of both the skin and mucous membranes. Specialized function of the pyramidal cell of the brain

of the brain, as well as the muscle cells of the heart, excludes the possibility of division of these cells and makes it possible to understand the need for selection in the phylo- and ontogenesis of intracellular regeneration as the only form of restoration of this substrate.

Table 5 Forms of regeneration in organs and tissues of mammals (according to Sarkisov D.S., 1988)

These data refute the ideas that existed until recently about the loss of the ability of some mammalian organs and tissues to regenerate, about the “bad” and “good” regenerating human tissues, that there is an “inverse relationship law” between the degree of tissue differentiation and their ability to regenerate. . It has now been established that in the course of evolution the ability to regenerate in some tissues and organs did not disappear, but took on forms (cellular or intracellular) corresponding to their structural and functional originality (Sarkisov D.S., 1977). Thus, all tissues and organs have the ability to regenerate, only its forms are different depending on the structural and functional specialization of the tissue or organ.

Morphogenesis regenerative process consists of two phases - proliferation and differentiation. These phases are especially well expressed in the cellular form of regeneration. IN proliferation phase young, undifferentiated cells multiply. These cells are called cambial(from lat. cambium- exchange, change) stem cells And progenitor cells.

Each tissue is characterized by its own cambial cells, which differ in the degree of proliferative activity and specialization, however, one stem cell can be the ancestor of several types.

cells (for example, a stem cell of the hematopoietic system, lymphoid tissue, some cellular representatives of the connective tissue).

IN differentiation phase young cells mature, their structural and functional specialization occurs. The same change of hyperplasia of ultrastructures by their differentiation (maturation) underlies the mechanism of intracellular regeneration.

Regulation of the regenerative process. Among the regulatory mechanisms of regeneration, humoral, immunological, nervous, and functional ones are distinguished.

Humoral mechanisms are implemented both in the cells of damaged organs and tissues (interstitial and intracellular regulators) and beyond (hormones, poetins, mediators, growth factors, etc.). The humoral regulators are keylons (from Greek. chalainino- weaken) - substances that can suppress cell division and DNA synthesis; they are tissue specific. Immunological mechanisms regulation is associated with "regenerative information" carried by lymphocytes. In this regard, it should be noted that the mechanisms of immunological homeostasis also determine structural homeostasis. Nervous mechanisms regenerative processes are associated primarily with the trophic function of the nervous system, and functional mechanisms- with a functional "request" of an organ, tissue, which is considered as a stimulus for regeneration.

The development of the regenerative process largely depends on a number of general and local conditions or factors. TO general should include age, constitution, nutritional status, metabolic and hematopoietic status, local - the state of innervation, blood and lymph circulation of the tissue, the proliferative activity of its cells, the nature of the pathological process.

Classification. There are three types of regeneration: physiological, reparative and pathological.

Physiological regeneration occurs throughout life and is characterized by constant renewal of cells, fibrous structures, the main substance of connective tissue. There are no structures that would not undergo physiological regeneration. Where the cellular form of regeneration dominates, cell renewal takes place. So there is a constant change of the integumentary epithelium of the skin and mucous membranes, the secretory epithelium of the exocrine glands, the cells lining the serous and synovial membranes, the cellular elements of the connective tissue, erythrocytes, leukocytes and blood platelets, etc. In tissues and organs where the cellular form of regeneration is lost, for example, in the heart, brain, intracellular structures are renewed. Along with the renewal of cells and subcellular structures, biochemical regeneration, those. renewal of the molecular composition of all body components.

Reparative or restorative regeneration observed in various pathological processes leading to damage to cells and tissues

her. The mechanisms of reparative and physiological regeneration are the same, reparative regeneration is enhanced physiological regeneration. However, due to the fact that reparative regeneration is induced by pathological processes, it has qualitative morphological differences from the physiological one. Reparative regeneration can be complete or incomplete.

complete regeneration, or restitution, characterized by the compensation of the defect with tissue that is identical to the deceased. It develops predominantly in tissues where cellular regeneration predominates. Thus, in the connective tissue, bones, skin, and mucous membranes, even relatively large defects in an organ can be replaced by a tissue identical to the deceased by cell division. At incomplete regeneration, or substitutions, the defect is replaced by connective tissue, a scar. Substitution is characteristic of organs and tissues in which the intracellular form of regeneration predominates, or it is combined with cellular regeneration. Since during regeneration there is a restoration of a structure capable of performing a specialized function, the meaning of incomplete regeneration is not in replacing the defect with a scar, but in compensatory hyperplasia elements of the remaining specialized tissue, the mass of which increases, i.e. going on hypertrophy fabrics.

At incomplete regeneration, those. tissue healing by a scar, hypertrophy occurs as an expression of the regenerative process, therefore it is called regeneration, it contains the biological meaning of reparative regeneration. Regenerative hypertrophy can be carried out in two ways - with the help of cell hyperplasia or hyperplasia and hypertrophy of cellular ultrastructures, i.e. cell hypertrophy.

Restoration of the initial mass of the organ and its function due mainly to cell hyperplasia occurs with regenerative hypertrophy of the liver, kidneys, pancreas, adrenal glands, lungs, spleen, etc. Regenerative hypertrophy due to hyperplasia of cellular ultrastructures characteristic of the myocardium, brain, i.e. those organs where the intracellular form of regeneration predominates. In the myocardium, for example, along the periphery of the scar that replaced the infarction, the size of the muscle fibers increases significantly; they hypertrophy due to hyperplasia of their subcellular elements (Fig. 81). Both ways of regenerative hypertrophy do not exclude each other, but, on the contrary, often are combined. So, with regenerative hypertrophy of the liver, not only an increase in the number of cells in the part of the organ preserved after damage occurs, but also their hypertrophy, due to hyperplasia of ultrastructures. It cannot be ruled out that regenerative hypertrophy in the heart muscle can proceed not only in the form of fiber hypertrophy, but also by increasing the number of their constituent muscle cells.

The recovery period is usually not limited only to the fact that reparative regeneration unfolds in the damaged organ. If

Rice. 81. Regeneration myocardial hypertrophy. Hypertrophied muscle fibers are located along the periphery of the scar

the effect of the pathogenic factor stops before the death of the cell, there is a gradual restoration of damaged organelles. Consequently, the manifestations of the reparative reaction should be expanded by including restorative intracellular processes in dystrophically altered organs. The generally accepted opinion about regeneration only as the final stage of the pathological process is hardly justified. Reparative regeneration is not local, A general reaction organism, covering various organs, but fully realized only in one or another of them.

ABOUT pathological regeneration they say in those cases when, as a result of various reasons, there is perversion of the regenerative process, violation of phase change proliferation

and differentiation. Pathological regeneration is manifested in excessive or insufficient formation of regenerating tissue (hyper- or hyporegeneration), as well as in the transformation during the regeneration of one type of tissue into another [metaplasia - see. Processes of adaptation (adaptation) and compensation]. Examples are hyperproduction of connective tissue with the formation keloid, excessive regeneration of peripheral nerves and excessive callus formation during fracture healing, sluggish wound healing and epithelial metaplasia in the focus of chronic inflammation. Pathological regeneration usually develops with violations of general And local regeneration conditions(violation of innervation, protein and vitamin starvation, chronic inflammation, etc.).

Regeneration of individual tissues and organs

Reparative regeneration of blood differs from physiological regeneration primarily in its greater intensity. In this case, active red bone marrow appears in the long bones in place of fatty bone marrow (myeloid transformation of fatty bone marrow). Fat cells are replaced by growing islands of hematopoietic tissue, which fills the medullary canal and looks juicy, dark red. In addition, hematopoiesis begins to occur outside the bone marrow - extramedullary, or extramedullary, hematopoiesis. Ocha-

GI extramedullary (heterotopic) hematopoiesis as a result of eviction from the bone marrow of stem cells appear in many organs and tissues - the spleen, liver, lymph nodes, mucous membranes, fatty tissue, etc.

Blood regeneration can be sharply oppressed (eg, radiation sickness, aplastic anemia, aleukia, agranulocytosis) or perverted (eg, pernicious anemia, polycythemia, leukemia). At the same time, immature, functionally defective and rapidly collapsing formed elements enter the blood. In such cases, one speaks of pathological regeneration of blood.

The reparative capabilities of the organs of the hematopoietic and immunocompetent systems are ambiguous. Bone marrow has very high plastic properties and can be restored even with significant damage. The lymph nodes they regenerate well only in those cases when the connections of the afferent and efferent lymphatic vessels with the surrounding connective tissue are preserved. Tissue regeneration spleen when damaged, it is usually incomplete, the dead tissue is replaced by a scar.

Regeneration of blood and lymph vessels proceeds ambiguously depending on their caliber.

microvessels have a greater ability to regenerate than large vessels. New formation of microvessels can occur by budding or autogenously. During vascular regeneration by budding (Fig. 82) lateral protrusions appear in their wall due to intensively dividing endothelial cells (angioblasts). Strands are formed from the endothelium, in which gaps appear and blood or lymph from the "mother" vessel enters them. Other elements: the vascular wall is formed due to the differentiation of the endothelium and connective tissue cells surrounding the vessel. Nerve fibers from preexisting nerves grow into the vascular wall. Autogenic neoplasm vessels consists in the fact that foci of undifferentiated cells appear in the connective tissue. In these foci, gaps appear, into which pre-existing capillaries open and blood flows out. Young connective tissue cells differentiate and form the endothelial lining and other elements of the vessel wall.

Rice. 82. Vessel regeneration by budding

Large vessels do not have sufficient plastic properties. Therefore, if their walls are damaged, only the structures of the inner shell, its endothelial lining, are restored; elements of the middle and outer shells are usually replaced by connective tissue, which often leads to narrowing or obliteration of the vessel lumen.

Connective tissue regeneration begins with the proliferation of young mesenchymal elements and neoplasms of microvessels. A young connective tissue rich in cells and thin-walled vessels is formed, which has a characteristic appearance. This is a juicy dark red fabric with a granular surface, as if strewn with large granules, which was the basis for calling it granulation tissue. Granules are loops of newly formed thin-walled vessels protruding above the surface, which form the basis of granulation tissue. Between the vessels there are many undifferentiated lymphocyte-like cells of the connective tissue, leukocytes, plasma cells and labrocytes (Fig. 83). Later on, it happens maturation granulation tissue, which is based on the differentiation of cellular elements, fibrous structures, and also vessels. The number of hematogenous elements decreases, and fibroblasts - increases. In connection with the synthesis of collagen fibroblasts in the intercellular spaces are formed argyrophilic(see Fig. 83), and then collagen fibers. The synthesis of glycosaminoglycans by fibroblasts serves to form

basic substance connective tissue. As fibroblasts mature, the number of collagen fibers increases, they are grouped into bundles; at the same time, the number of vessels decreases, they differentiate into arteries and veins. The maturation of granulation tissue ends with the formation coarse fibrous scar tissue.

New formation of connective tissue occurs not only when it is damaged, but also when other tissues are incompletely regenerated, as well as during organization (encapsulation), wound healing, and productive inflammation.

The maturation of granulation tissue may have certain deviations. Inflammation that develops in the granulation tissue leads to a delay in its maturation,

Rice. 83. granulation tissue. There are many undifferentiated connective tissue cells and argyrophilic fibers between the thin-walled vessels. Silver impregnation

and excessive synthetic activity of fibroblasts - to excessive formation of collagen fibers with their subsequent pronounced hyalinosis. In such cases, scar tissue appears in the form of a tumor-like formation of a bluish-red color, which rises above the surface of the skin in the form keloid. Keloid scars are formed after various traumatic skin lesions, especially after burns.

Regeneration of adipose tissue occurs due to the neoplasm of connective tissue cells, which turn into fat (adiposocytes) by accumulating lipids in the cytoplasm. Fat cells are folded into lobules, between which there are connective tissue layers with vessels and nerves. Regeneration of adipose tissue can also occur from the nucleated remnants of the cytoplasm of fat cells.

Bone regeneration in case of bone fracture, it largely depends on the degree of bone destruction, the correct reposition of bone fragments, local conditions (circulatory status, inflammation, etc.). At uncomplicated bone fracture, when bone fragments are motionless, may occur primary bone union(Fig. 84). It begins with growing into the area of ​​the defect and hematoma between bone fragments of young mesenchymal elements and vessels. There is a so-called preliminary connective tissue callus, in which bone formation begins immediately. It is associated with the activation and proliferation osteoblasts in the area of ​​damage, but primarily in the periostat and endostat. In the osteogenic fibroreticular tissue, low-calcified bone trabeculae appear, the number of which increases.

Formed preliminary callus. In the future, it matures and turns into a mature lamellar bone - this is how

Rice. 84. Primary bone fusion. Intermediary callus (shown by an arrow), soldering bone fragments (according to G.I. Lavrishcheva)

definitive callus, which in its structure differs from bone tissue only in the disorderly arrangement of the bone crossbars. After the bone begins to perform its function and a static load appears, the newly formed tissue undergoes restructuring with the help of osteoclasts and osteoblasts, bone marrow appears, vascularization and innervation are restored. In case of violation of local conditions of bone regeneration (circulatory disorder), mobility of fragments, extensive diaphyseal fractures, secondary bone union(Fig. 85). This type of bone fusion is characterized by the formation between bone fragments, first of cartilage tissue, on the basis of which bone tissue is built. Therefore, with secondary bone fusion they speak of preliminary osteochondral callus, which develops into mature bone over time. Secondary bone fusion compared with the primary is much more common and takes longer.

At adverse conditions bone regeneration may be impaired. Thus, when a wound becomes infected, bone regeneration is delayed. Bone fragments, which, during the normal course of the regenerative process, act as a framework for the newly formed bone tissue, support inflammation under conditions of wound suppuration, which inhibits regeneration. Sometimes primary bone-cartilaginous callus is not differentiated into bone callus. In these cases, the ends of the broken bone remain movable, forming false joint. Excess production of bone tissue during regeneration leads to the appearance of bone outgrowths - exostoses.

Cartilage regeneration in contrast to the bone occurs usually incomplete. Only small defects can be replaced by newly formed tissue due to the cambial elements of the perichondrium - chondroblasts. These cells create the basic substance of cartilage, then turn into mature cartilage cells. Large cartilage defects are replaced by scar tissue.

regeneration of muscle tissue, its possibilities and forms are different depending on the type of this fabric. Smooth mice, whose cells are capable of mitosis and amitosis, with minor defects can regenerate quite completely. Significant areas of damage to smooth muscles are replaced by a scar, while the remaining muscle fibers undergo hypertrophy. New formation of smooth muscle fibers can occur by transformation (metaplasia) of connective tissue elements. This is how bundles of smooth muscle fibers are formed in pleural adhesions, in thrombi undergoing organization, in vessels during their differentiation.

striated muscles regenerate only when the sarcolemma is preserved. Inside the tubes from the sarcolemma, its organelles are regenerated, resulting in the appearance of cells called myoblasts. They stretch, the number of nuclei in them increases, in the sarcoplasm

Rice. 85. Secondary bone fusion (according to G.I. Lavrishcheva):

a - osteocartilaginous periosteal callus; a piece of bone tissue among the cartilage (microscopic picture); b - periosteal bone and cartilage callus (histotopogram 2 months after surgery): 1 - bone part; 2 - cartilaginous part; 3 - bone fragments; c - periosteal callus soldering displaced bone fragments

myofibrils differentiate, and the sarcolemma tubes turn into striated muscle fibers. Skeletal muscle regeneration may also be associated with satellite cells, which are located under the sarcolemma, i.e. inside the muscle fiber, and are cambial. In the event of an injury, satellite cells begin to divide intensively, then undergo differentiation and ensure the restoration of muscle fibers. If, when the muscle is damaged, the integrity of the fibers is violated, then at the ends of their ruptures, flask-shaped bulges appear, which contain a large number of nuclei and are called muscle kidneys. In this case, the restoration of the continuity of the fibers does not occur. The rupture site is filled with granulation tissue, which turns into a scar (muscle callus). Regeneration heart muscles when it is damaged, as with damage to the striated muscles, it ends with scarring of the defect. However, in the remaining muscle fibers, intense hyperplasia of ultrastructures occurs, which leads to fiber hypertrophy and restoration of organ function (see Fig. 81).

Epithelial regeneration in most cases, it is carried out quite completely, since it has a high regenerative capacity. Regenerates especially well cover epithelium. Recovery keratinized stratified squamous epithelium possible even with fairly large skin defects. During the regeneration of the epidermis at the edges of the defect, there is an increased reproduction of cells of the germinal (cambial), germ (Malpighian) layer. The resulting epithelial cells first cover the defect in one layer. In the future, the layer of the epithelium becomes multi-layered, its cells differentiate, and it acquires all the signs of the epidermis, which includes the growth, granular shiny (on the soles and palmar surface of the hands) and the stratum corneum. In violation of the regeneration of the skin epithelium, non-healing ulcers are formed, often with the growth of atypical epithelium in their edges, which can serve as the basis for the development of skin cancer.

Integumentary epithelium of mucous membranes (stratified squamous non-keratinizing, transitional, single-layer prismatic and multinuclear ciliated) regenerates in the same way as multi-layered squamous keratinizing. The defect of the mucous membrane is restored due to the proliferation of cells lining the crypts and excretory ducts of the glands. Undifferentiated flattened epithelial cells first cover the defect with a thin layer (Fig. 86), then the cells take the form characteristic of the cellular structures of the corresponding epithelial lining. In parallel, the glands of the mucous membrane are partially or completely restored (for example, tubular glands of the intestine, endometrial glands).

Mesothelial regeneration the peritoneum, pleura and pericardial sac is carried out by dividing the remaining cells. Comparatively large cubic cells appear on the surface of the defect, which then flatten. With small defects, the mesothelial lining is restored quickly and completely.

The state of the underlying connective tissue is important for the restoration of the integumentary epithelium and mesothelium, since the epithelialization of any defect is possible only after it has been filled with granulation tissue.

Regeneration of specialized organ epithelium(liver, pancreas, kidneys, endocrine glands, pulmonary alveoli) is carried out according to the type regenerative hypertrophy: in areas of damage, the tissue is replaced by a scar, and along its periphery, hyperplasia and hypertrophy of parenchyma cells occur. IN liver the site of necrosis is always subject to scarring, however, in the rest of the organ, intensive neoplasm of cells occurs, as well as hyperplasia of intracellular structures, which is accompanied by their hypertrophy. As a result, the initial mass and function of the organ are quickly restored. The regenerative possibilities of the liver are almost limitless. In the pancreas, regenerative processes are well expressed both in the exocrine sections and in the pancreatic islets, and the epithelium of the exocrine glands becomes the source of restoration of the islets. IN kidneys with necrosis of the epithelium of the tubules, the surviving nephrocytes reproduce and restore the tubules, but only with the preservation of the tubular basement membrane. When it is destroyed (tubulorhexis), the epithelium is not restored and the tubule is replaced by connective tissue. The dead tubular epithelium is not restored even in the case when the vascular glomerulus dies along with the tubule. At the same time, scar connective tissue grows in place of the dead nephron, and the surrounding nephrons undergo regenerative hypertrophy. in the glands internal secretion recovery processes are also represented by incomplete regeneration. IN lung after the removal of individual lobes, hypertrophy and hyperplasia of tissue elements occur in the remaining part. Regeneration of the specialized epithelium of organs can proceed atypically, which leads to the growth of connective tissue, structural reorganization and deformation of organs; in such cases one speaks of cirrhosis (liver cirrhosis, nephrocyrrhosis, pneumocirrhosis).

Regeneration of different parts of the nervous system happens ambiguously. IN head And spinal cord neoplasms of ganglion cells do not

Rice. 86. Regeneration of the epithelium in the bottom of a chronic stomach ulcer

even when they are destroyed, the restoration of function is possible only due to the intracellular regeneration of the remaining cells. Neuroglia, especially microglia, are characterized by a cellular form of regeneration; therefore, defects in the tissue of the brain and spinal cord are usually filled with proliferating neuroglia cells - so-called glial (glial) scarring. When damaged vegetative nodes along with hyperplasia of cell ultrastructures, their neoplasm also occurs. In case of violation of integrity peripheral nerve regeneration occurs due to the central segment, which has retained its connection with the cell, while the peripheral segment dies. The multiplying cells of the Schwann sheath of the dead peripheral segment of the nerve are located along it and form a case - the so-called Byungner cord, into which regenerating axial cylinders from the proximal segment grow. The regeneration of nerve fibers ends with their myelination and restoration of nerve endings. Regenerative hyperplasia receptors pericellular synaptic devices and effectors is sometimes accompanied by hypertrophy of their terminal apparatuses. If the regeneration of the nerve is disturbed for one reason or another (significant divergence of parts of the nerve, the development of an inflammatory process), then a scar is formed at the site of its break, in which the regenerated axial cylinders of the proximal segment of the nerve are randomly located. Similar growths occur at the ends of the cut nerves in the stump of the limb after its amputation. Such growths formed by nerve fibers and fibrous tissue are called amputation neuromas.

Wound healing

Wound healing proceeds according to the laws of reparative regeneration. The rate of wound healing, its outcomes depend on the degree and depth of wound damage, the structural features of the organ, the general condition of the body, and the methods of treatment used. According to I.V. Davydovsky, the following types of wound healing are distinguished: 1) direct closure of an epithelial cover defect; 2) healing under the scab; 3) wound healing by primary intention; 4) wound healing by secondary intention, or wound healing through suppuration.

Direct closure of an epithelial defect- this is the simplest healing, which consists in the creeping of the epithelium on the superficial defect and closing it with an epithelial layer. Observed on the cornea, mucous membranes healing under the scab concerns small defects, on the surface of which a drying crust (scab) quickly appears from coagulated blood and lymph; the epidermis is restored under the crust, which disappears 3-5 days after the injury.

Healing by primary intention (per rimamm intentionem) observed in wounds with damage not only to the skin, but also to the underlying tissue,

and the edges of the wound are even. The wound is filled with clots of spilled blood, which protects the edges of the wound from dehydration and infection. Under the influence of proteolytic enzymes of neutrophils, a partial lysis of blood coagulation, tissue detritus occurs. Neutrophils die, they are replaced by macrophages that phagocytize red blood cells, the remnants of damaged tissue; hemosiderin is found in the edges of the wound. Part of the contents of the wound is removed on the first day of injury along with exudate on its own or when treating the wound - primary cleansing. On the 2-3rd day, fibroblasts and newly formed capillaries growing towards each other appear at the edges of the wound, granulation tissue, the layer of which at primary tension does not reach large sizes. By the 10-15th day, it fully matures, the wound defect epithelizes and the wound heals with a delicate scar. In a surgical wound, healing by primary intention is accelerated due to the fact that its edges are pulled together with silk or catgut threads, around which giant cells of foreign bodies that absorb them accumulate and do not interfere with healing.

Healing by secondary intention (per secundam intentionem), or healing through suppuration (or healing by granulation - per granulationem), It is usually observed with extensive wounds, accompanied by crushing and necrosis of tissues, penetration of foreign bodies and microbes into the wound. At the site of the wound, hemorrhages occur, traumatic swelling of the edges of the wound, signs of demarcation quickly appear. purulent inflammation on the border with dead tissue, melting of necrotic masses. During the first 5-6 days, rejection of necrotic masses occurs - secondary cleansing of the wound, and granulation tissue begins to develop at the edges of the wound. granulation tissue, performing the wound, consists of 6 layers passing into each other (Anichkov N.N., 1951): superficial leukocyte-necrotic layer; superficial layer of vascular loops, layer of vertical vessels, maturing layer, layer of horizontally located fibroblasts, fibrous layer. The maturation of granulation tissue during wound healing by secondary intention is accompanied by regeneration of the epithelium. However, with this type of wound healing, a scar is always formed in its place.

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 the control of cell activity with the help of light.

The ultimate goal of all such research is to discover the natural mechanisms that control the recovery of body parts, and learn how to turn them on in humans. Tadpoles are the best 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 the tail is cut off from individuals that have entered the so-called refractory period, they will no longer be able to grow it again.

The internal systems that control regeneration are still present in their body, but for some reason they have been stopped. Michael Levin (Michael Levin) and colleagues forced them to work again, in fact, turning back physiological time.

It's amazing how they did it. One group of tailless tadpoles was reared in a container illuminated by short flashes of light for two days; the other lived in total darkness. As a result, full-fledged tail tissue was restored in the tadpoles of the first group, including the structures of the spine, muscles, nerve endings, and skin. The second tadpoles could not overcome the consequences of amputation, as it should be at their age.

If this looks like a trick, then only partly. To understand why this happened, it is necessary to explain the principle underlying the experiment. Indeed, all animals at the same stage of the life cycle were subjected to identical manipulations. The only difference between the two groups was the presence or absence of lighting. However, the light was not the true cause of the changes that occurred. It served as a remote switch that actuated a factor that (in a not entirely clear way) triggered the regeneration process. Hyperpolarization of transmembrane potentials of cells acted as such a factor; or more simply - bioelectricity.

Optogenetics makes it relatively easy to construct an experiment. The mRNA molecules of the photosensitive 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. Under the condition of stimulation with light (and only in this case), they induced a current of ions through the membrane, thereby changing its electric potential.

In fact, apart from light-activated membrane pumps, scientists have offered nothing to help tadpoles. However, only one effect on the electrical properties of cells was enough to start a complex cascade of regeneration 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 a light on the tadpole.

Regeneration remains one of the major mysteries of biology. In 2005, the journal Science included the following question among the 25 most important problems 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 a hand.

It 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 is possible to revive it again in an adult. At the moment, most biologists' research is centered around gene expression or chemical signals. Michael Levine's lab hopes to find the answer to the mystery of regeneration in another phenomenon, bioelectricity, and those hopes appear to be justified.

The fact that electric currents are present in a living organism has been known since the experiments of Galvani. However, few have studied their impact on development as closely as Levin does. Bioelectricity has long had a chance to become a worthy topic of experiments, but the molecular revolution in biology in the second half of the 20th 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 his predecessors did not have, 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 an organism.

By changing the transmembrane potential of the cells, the scientist can instruct the tissues of the tadpole to grow an eye in a predetermined area of ​​the body. A photograph of a six-legged frog hangs on the wall of his laboratory. Additional limbs appeared in her solely as a result of exposure to electrical biocurrents. Unlike neurons, ordinary cells are not able to fire, but they can consistently transmit signals throughout almost the entire body through gap junctions. If a planaria, a tiny worm that can regenerate, is cut off the tail, a request will be sent from the cut area to the head in order to make sure 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 obtained worms with two heads, two tails, and even worms with an unusual design with four heads. Levin said he was almost always told that his ideas weren't supposed to work. He relied on his intuition, and in most cases it did not fail.

From these attempts it is still very far from full knowledge of how to restore a limb in a person. So far, disabled people can only count on the improvement of prostheses. But in Tufts University's unique lab, they're looking for something even more fundamental: Like the genetic code, Levine argues, 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. Lewin considers them as a consequence of the loss of information about the shape of the body by cells, and the study of the problem of cancer is one of the tasks of his laboratory. As is often the case, apparently different processes can have a single nature.

If the bioelectric code is really behind the construction of various organs of the body, its solution can shed light on two of the most important problems facing humanity at once.

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REGENERATION , the process of formation of a new organ or tissue at the site of a part of the body removed in one way or another. Very often, R. is defined as the process of restoring the lost, i.e., the formation of an organ similar to the removed one. Such a definition, however, comes from a false teleological point of view. First of all, the part of the organism that arises during R. is never completely identical with the previously existing one, it always differs from it in one way or another (Schaxel). Then the fact of formation instead of a remote site of absolutely other, dissimilar to it is enough known. The corresponding phenomenon is also attributed to R., however, calling it atypical R. However, there is no evidence that the prog-processes available here essentially differ in anything from other types of R. Thus, it would be more correct to define R. in the above way. . Classification of phenomena R. There are two main types of regenerative processes: physiological and reparative R. Physiological R. takes place in that. the case when the process occurs without the presence of any special influence from the outside. R. of this kind are phenomena of periodic molting of birds, mammals, and other animals, a change in the desquamating human skin epithelium, and also the replacement of dying cells of glands and other formations with new cells. Reparative R. includes cases of neoplasm as a result of receiving by the body of one or another damage, both as a result of artificial intervention, and regardless of this. The phenomena of reparative R., as the most studied, will be mainly stated below. Depending on the final result of the process, reparative R. is divided into typical, when the formed organ b. or m. similar to pre-existing, and atypical when there is no such similarity. Deviations from the typical course of R. may consist either in the formation of a completely different organ instead of a pre-existing organ or in its modification. In the case when the appearance of another organ is associated with a perversion of polarity, for example. when the head end of the worm regenerates instead of the cut off tail end, the phenomenon is called heteromorphosis. The modification of an organ can be expressed in the presence of any additional parts up to doubling or tripling of the organ, or in the absence of usually characteristic formations. “It should be remembered that the division of R. into typical and atypical, based on a teleological view and focusing on a pre-existing organ, does not reflect the essence of phenomena and is completely arbitrary. The ability to R. is an extremely widespread phenomenon both among animals and among plants, although individual species differ from each other both in the degree of regenerative ability and in the course of the process itself. In general, we can assume that the higher the organization of the organism, the lower its regenerative capacity; however, there are a number of exceptions to this rule. Thus, many # related species differ very strongly from each other in terms of regenerative manifestations. On the other hand, a number of higher species are more capable of regeneration than lower ones. In an amphibian, for example, even individual organs, such as a tail and a limb, can regenerate while some worms (Nematoda) are distinguished by the almost complete absence of R. As a rule, however, the greatest ability for R. is found among lower animals. Unicellular are characterized by a strongly pronounced regenerative ability (Fig. 1). In some species, pieces equal to one hundredth of a of an animal, are capable of restoring it entirely. Among multicellular organisms, intestinal cavities and worms are distinguished by the greatest regenerative capacity. Some hydroids restore an animal from one two hundredth of its part. Worms (especially Annelida and Turbellaria) from several segments can form all the missing parts. Not much inferior to these species such a high-ranking group as tunicates, where „ “R. of the whole animal can take place from one part of it (for example, the gill basket in Clavellina). The regenerative ability is also well expressed in some echinoderms; so, starfish form a whole belly- Rice - ! Infusoria regeneration ttpa ich ptttpgp ttv Stentor, cut into three parts nee from one lusti (According to the korshe^y.) cha (Fig. 2). The regenerative capacity of mollusks and arthropods is significantly reduced. Here, only individual appendages of the body can regenerate: limbs, tentacles, etc. Of vertebrate animals, regenerative phenomena are best expressed in fish and amphibians. Even in reptiles, the regeneration of the tail and tail-like appendages in place of the limbs is possible; in birds, only the beak regenerates from the "outer parts"

Figure 2. Regeneration of starfish Linckia mul-

Tifofa from one beam. successive stages of regeneration. (According to Korschelt.) And integuments. Finally, mammals, including humans, are capable of replacing only small areas of organs and skin lesions. The regenerative capacity does not remain equally pronounced throughout the life of the individual: the various stages of development differ in this respect, each with its own characteristic features. As a rule, it can be said that the younger the animal, the higher its regenerative capacity. A tadpole, for example, can regenerate limbs in the early stages of development, while entering the period of metamorphosis, it loses this ability. This general rule has, however, a number of exceptions. There are cases when an earlier stage of development has a lower regenerative capacity. Planarian larvae are less developed 685 REGENERATION 536 Tie regeneration phenomena in comparison with adult animals (Steinmann), the same takes place for the larvae of some other animals. Already from the foregoing it could be seen that different areas of the body differ from each other in their regenerative capacity. Weisman accepted that the ability of R. depends R n "and ([ [ | | | ([ | on how much this part is susceptible to the danger of damage, and the greater the latter, the greater the regenerative ability, a property developed as a result of natural selection. However, later studies have shown that such a pattern does not 6,6 15 6,9 10 7,2 5 ■ ■\ g°\ /i [^ 1 * .u/"" h > *■-.„ 8 S 12 14 Figure 3. Solid line - change in the intensity of mitogenetic radiation of the regenerating tail of an axolotl. H? ordinal units of radiation intensity. Dashed line - changes in the active reaction of the tissues of the regenerating limb of the axolotl. On the ordinate is the pH value (this may be tired Okunev). On the. abscissa - days NGSh7TRTTYA. ^„^ pl-regeneration. (From Blyakher and Noyalen. row op. Bromley.) gangs, not subject to usually susceptible to damage during the free life of the individual and well protected, nevertheless has a high regenerative capacity (Morgan, Przibfam). Ubisch connects regenerative phenomena with the differentiation of the organism; in his opinion, the previously developing parts cease to regenerate with age, or their R. is less intense. Thus, in amphibians, where organs that lie more anteriorly differentiate earlier, an appropriate R. gradient can be established - from front to back. Ubisch's statements, which are supported by a number of data, still need further confirmation on more material. On some species (mainly on worms), Child and his collaborators have established a certain R. gradient in the same way with respect to the longitudinal axis of the body, but its direction does not always go from front to back, but is associated with more complex patterns. Child considers that this gradient depends on degree fiziol. activity in various parts of the body. Lower organized animals have the ability to regenerate both parts located proximal to the amputation site and

Figure 4. Regeneration of an amputated forelimb in a salamander after */ 4 (a) and 12 (b) hours, a: i-blastema cells; 2 - shoulder stump; 3 -nerve; 4 -epidermis; b: 1- blastema cells; 2 -cartilage; 3-epidermis; 4 - shoulder stump.

located distally. In higher animals, only the latter regenerate. In amphibians, for example. an organ, even transplanted in an inverted position, regenerates the same formation as in the normal position.

Figure 5.:Regenerap*yag "am-

The course of the regeneration process. The regeneration process proceeds differently depending on which organism we are dealing with and what part of it is being removed. As an example, consider the most studied object, R. amphibian limbs. In this case, the following phenomena take place. After amputation of the organ, the edges converge wounds due to contraction of the cut muscles.The blood on the surface of the wound coagulates, releasing fibrin threads. pb- chrrrz 8 days: J and 2 - blah " damaged tissue oostemalcells; h- epi- razuet on the wound PO-dermis; 4 - shoulder stump. upper scab. As a result of tissue damage and the impact of the external environment on the surface unprotected by the skin, decay processes occur in the organ. The latter are revealed in a change in the acidity of the regenerate (a decrease in pH from 7.2 to 6.8, Okunev) and the appearance of mitogenetic radiation (Blyakher and Bromley). However, the wound surface does not remain unprotected for a long time: already within the next few hours, the process of epithelium creeping from the wound edges is observed, as a result of which an epithelial film is formed on the wound surface. Under this epithelial cover, all further processes take place, leading to the destruction niyu and restructuring of the old and the formation of a new body. These processes are expressed, on the one hand, in the ongoing decay. 1 -giant cells; tr gigt irrittp-2-blastema cells; l-nude-te gist "isole l and cha shoulder; 4 - musculature; 5- Vania, SHOW-epidermis. The breakdown is especially strong in the period from 5 to 10 days, starting from the moment of amputation, when it apparently reaches its greatest intensity. Physiological indicators also testify to this. Okunev * found the greatest acidity on 5th day, when pH = 6.6 The intensity of mitogenetic radiation also increases simultaneously compared to the previous days (Bromley) The curves of the increase in acidity and intensity of mitogenetic radiation turn out to be parallel to each other throughout the regeneration. the tops of the maximum are on the 1st and 5th day of R. (Fig. 3).Along with this, new-forming processes are clearly indicated already in the first week of R. They affect mainly in the formation under the epithelial film of growth from homogeneous cells, called blastema The development of a new organ is predominantly

Figure 7. Regeneration of am-

■ directly due to blastema cells (Fig. 4-7). After a certain period of growth, differentiation of individual parts occurs in the regenerate. In this case, the more proximal parts are differentiated first, and then the distal ones. In this regard, not all organisms process the same way. In some animals, the ratios ^100!%ch can even be reversed, Fiziol. the features of the regenerate are final - 2 but not those of the formed organ. This is manifested in particular 11 in the fact that the regenerate has histolyzing properties. In the event that its surface comes into contact with other tissues, for example. when closing the regenerate coputed with the "ANTERIOR FLATT", the salamander's foot-extremity develops HISTOLYSIS AFTER-STE P m ^ \ Te e tki / 2 "-gi: them (Bromley and Orechoganth cells; h- epivic). You shouldn't think dermis; 4- muscles; that R. Skaeyva's process is a 5-shoulder ring; 6 "- p _ tgpkp on the amggeti-stump of the shoulder. (Only Hcl is corrugated amiush shelt.) a regenerating organ. It has its effect on the rest of the body, which can manifest itself in various ways. So, a change can be detected in the blood of an animal, the mitogenetic radiation of which deviates from normal intensity, and these fluctuations have a characteristic curve. When R., hydras show a breakdown of organs that are not in close proximity to the regenerate, namely germ cells, moreover, predominantly male (Goetsch). Influence of R. also affects the growth and other properties of the organism - a phenomenon, mostly described under the name of regulation. Material of the regenerate. The question of the material, due to which the formation of the regenerate occurs, should be resolved differently depending on the type of the animal and the nature of the damage inflicted. If it is a question of damage to any one tissue, then usually the process proceeds due to the growth of the remainder of the corresponding tissue. The situation is more complicated in the case of R. of an organ or the restoration of the organism from a separate section of it. However, it can be established that that basically, at least in amphibians, R. comes from the material immediately adjacent to the wound surface, and not due to cells coming from other areas of the body. This is shown by R. olyts of the haploid limb of a newt transplanted into a diploid nuclear animal. The resulting regenerate consists of haploid nuclear cells (Hertwig). The same follows from the transplantation of limbs from the black race of axolotls to the white, when the regenerating limb turns out to be black. The facts atl exclude the idea of ​​R. due to the various cellular elements that come with the blood stream. When considering the material going to R., one has to reckon with a twofold possibility. R. can occur either at the expense of the so-called. reserve, indifferent cells that remain undifferentiated during embryonic development, or there is a use of already specialized

fallen cellular elements. The importance of reserve cells has been shown in a number of animals. So, R. in hydras occurs mainly due to the so-called. interstitial cells. The same is true of turbellarians. Among the annuli, this role belongs to neoblasts belonging to elements of the same kind. In ascidia, indifferent cells also play an important role in R. The situation is more complicated in vertebrates, where various authors attribute the main role in R. to different tissues. Although here there are indications of the origin of blastema cells from non-specialized elements, this fact cannot be considered firmly established. Nevertheless, the provisions of the previously dominant theory of Gewebe-sprossung, which recognized the possibility of the development of cells of a tissue only from cells of a similar tissue, were fundamentally shaken. But if it is possible to accept the formation of a significant mass of the regenerate due to non-specialized cells, then this does not exclude the possibility of the development of part of the regenerate from differentiated elements. In this case, we can talk about both the development of tissues - due to the reproduction of elements of the same name, and the transition of cells of one type to another (metaplasia). In fact, in many cases it can be shown that both process. Thus, the musculature is usually Significant Figure 8. of undestroyed $ЖСЖ™?^ muscle cells. In rings, the formation of muscles from epithelial elements can be established. The same takes place in certain crayfish (Pribram). The formation of the nervous system from ectodermal cells has been established in ascidians (Schultze). In amphibians, it is known that R. lenses can originate from the edge of the iris (Wolff, Colucci). It is also possible to accept the formation of a cartilaginous and bone skeleton without the participation of cartilaginous and bone elements of a pre-existing organ.

Since the regeneration process includes both. development from indifferent elements, as well as the participation of specialized elements, then in each individual case a special study is needed to clarify the role of each of these processes in R. If we consider R. in amphibians as an example, again due to its greatest study, then the matter is presented here in the following form. Nerves are always formed due to the growth of the endings of old nerve trunks. The situation is different with bone tissue in the case of R. limbs. It has been shown that even with the removal of the entire bone skeleton of the limb, including the shoulder girdle, when such a boneless limb is amputated, R. of an organ with a skeleton occurs (Fritsch, 1911; Weiss, Bischler) (Fig. 8). The situation is different with R. tail. In this case, the bone parts are formed only when there is damage to the old skeletal parts in the area of ​​the regenerate, the shoulder girdle and shoulder; amputation above the elbow. The forearm with bones of the forearm and the hand with phalanges have been regenerated. Carpus still cartilaginous, radius and ulna shifted into boneless shoulder. (According to Kor-shelt.)

n bone elements of the last can take part in R. (fig., 9). Regarding the connective tissue part of the skin, the corium, we also have evidence of the possibility of its formation without the participation of the old corium a (Weiss). As for the muscles, the removal of most of the muscles of the limb did not lead to any anomalies in the development of the regenerate. In addition, in the case of transplanting a piece of notochord in Anura larvae into a region of the tail devoid of muscles, it was possible to induce the formation of a tail in this place with acc. direction of the tail cut. The resulting organ had musculature (Marcucci). However, histological studies show that with normal R. of the tail, its muscles are formed from the corresponding elements of the same old organ (NaVІlle). So. arr. a significant part of the regenerate in amphibians * may be formed not as a result of the reproduction of old tissues, but from the mass of the blastema, the origin of the elements of which, as already indicated, has not yet been sufficiently established. At the same time, there may be other relationships that we have with R. of the tail, the axial organs of the d-rogo regenerate only in the presence of old ones. At the same time, it should be noted that even R. of the same organ can come from different material depending on the conditions, as could be seen from the example of the formation of the muscular elements of the tail. The given experiences though also specify a possibility of development of nek-ry fabrics (eg bone) not from cells of similar fabric, do not resolve all the same a question of how the situation is under normal conditions R. In this direction further researches are necessary.

Conditions R.A. Regenerating area. The course of R., of course, is closely dependent on which part of the body is subjected to amputation and, consequently, in which area regenerative phenomena are played out. First of all, we can encounter the absence of R. in some parts of the body, or rather, with a weak expression of the corresponding phenomena. Philippo (Philippeau) discovered the absence of regeneration in the salamander in the case of the extirpation of a limb with the entire shoulder girdle. Schotte (Schotte) showed that the amputation of the tail is accompanied by regeneration only in that Figure 9. Radiograph of the regenerated tail of the lizard Lacerta muralis. Rupture in the region of the IV tail vertebra. (According to Korschelt.)

Figure 10. Triton cristats after complete removal of the tail area; no traces of regeneration within 8 months.

The case if the incision passes sufficiently distally (Fig. 10). Vallette and Guyenot note the lack of regeneration of the nasal parts of the head when too much area is amputated. In the same way, R., the eye does not occur with complete enucleation (Shak-sel). Gills do not regenerate when completely removed. Hyeno interprets these phenomena in such a way that R. can only occur

Figure 12. Anterior regeneration in an earthworm. The position of the regenerate is determined by the nerve trunk: 1- regeneration plane; 2-end of the cut nerve trunk.

Figure 11. Replacement of the left eye, removed together with the ophthalmic ganglion, by the antenna-like appendage (I): 2-supraesophageal ganglion; 3 - eye; 4- ocular ganglion. (According to Korschelt.) in the presence of certain cellular complexes, to-rye can be completely removed at a sufficient degree of damage. Reliable proof of this proposition, however, has not yet been given, and it is possible that in some cases the absence of regeneration discovered by the indicated authors is associated with other conditions. The nature of the formation that occurs during R. also depends on the regenerating site. It is well known that when various parts of the body are removed, various formations arise. However, this phenomenon should not be explained by the fact that the newly formed organ should be similar to the remote one. So, the experience of Herbst (Herbst), confirmed by other authors, is known, when, when an eye cancer is removed, the eye regenerates while leaving the optic ganglion, and with the simultaneous removal of the ganglion, R. antennas are observed (Fig. 11). During extirpation in one species of insect (Dixippus morosus) of the antennae, the formation of an antennae is observed in the distal part, while amputation at the base regenerates the limb. The corresponding phenomena are called homoiosis. It is clear that the speed of R. also depends on the regenerating site, as already mentioned. B. Parts of the amputated organ. As was seen from the experiments on removing the skeleton of a limb, R. can also occur in its absence. However, as Bishler has shown, at R. of boneless body regenerates not that segment, to-ry is exposed to amputation, but only more distal, so at R. eg. limb, an organ shortened by one segment arises. Since development is also observed in the absence of bone tissue, the relationship of R.'s specificity with the skeleton is denied. In addition, the transplantation of some bones in place of others, for example. hips in place of the shoulder, do not change the morphology of the regenerate. An important role in regenerative phenomena belongs to the nervous system. The necessity of the presence of neural connections for the formation of the regenerate has been proven, but not for all species. For a number of animals, such a law £54

dimension does not seem to exist. The clearest data are available for worms, echinoderms, and especially amphibians. In worms, Morgan showed the need for nerve endings in the area subjected to R. in order for the regeneration process to take place (Fig. 12). The same is shown for the starfish (Mor-gulis). However, there are data contradicting those just mentioned, so further research is needed in this direction. For amphibians, it has been shown that the presence of a central nervous system is not a necessary condition for P. (Barfurth, Rubin, Godlevsky). However, in case of violation of peripheral innervation Figure 13. Heterotope-regenerating organ the process of restoration of abduction of the shoulder is EXISTS. Having plexuses here. (According to Gie- the place of the relationship were you- n0 -)

Clear as a result of detailed experiments by Schotte and Weiss. Both of them showed that in the case of complete denervation, R. does not take place. Schotte showed that only the sympathizer matters. nervous system, because when transection of the sympathetic. nerves and leaving sensory and motor innervation, the formation of the organ does not occur. On the contrary, R. is evident while maintaining one sympathetic. innervation. The significance of the nervous system was proved by Schotte not only for adult animals, but also for larvae. Schotte's data regarding: sympathetic. innervations, however, raise objections from some authors who believe that the main role in the regeneration process belongs to the spinal ganglia (Locatelli). The data obtained also indicate that the role of the nervous system is not limited to the initial stages of the process; for R.'s continuation, the presence of the nervous system is also; necessary. A number of authors put the specificity of the regenerate in connection with the nervous system. In their opinion, there is a specific influence of the latter. Interesting data in favor of this assumption were given by Locatelli, who obtained the formation of additional limbs in newts by bringing the central end of the cut p. ischiadici to the surface of the body in the region of the flank and hind limb (Figure 13). However, Gieno and Schotte showed their research-; lcd, that the specificity of the nerves does not play a role in this phenomenon. It is true that bringing the cut end of the nerve to one or another area of ​​the Organism causes the formation of an organ here, but the nature of the organ is associated with the specificity of the area, and not the nerve. The same nerve, being brought to the area surrounding the hind limb, causes the development of the back here! her legs, and getting into the area located closer to the tail, causes the formation, namely the last organ. When bringing the nerve to the intermediate areas, you can get

Figure 14. Inhibited regeneration of the right hind limb of an axolotl due to the formation of a skin scar. (According to Kor-shelt.)

Read chimerical formations between tail and limb. A number of other data in favor of the specificity of the nervous system (Wolf, Walter) also received a different explanation. In this regard, the assumption of the specificity of the nervous influence on R. must be rejected. Removal of the skin at the site of amputation for a certain length leads to the fact that the R. Degeneration of the open area may also occur, and then R. begins from the moment when the degeneration of the area reaches the edge of the skin and the corresponding parts fall off. That. the presence of skin, or rather the epithelial cover, is a necessary condition for R. of the organ. This situation explains the absence of R. when closing the wound surface with a skin flap (Fig. 14), shown by a number of authors both in amphibians (Tornier, Shaksel, Godlevsky, Efimov) and insects (Shaksel and Adensamer). This phenomenon is due to the fact that the epithelium of the skin does not have access to the wound surface, being separated from it by the connective tissue part of the skin, but for the presence of R. it is necessary to cover the skin with young epithelium. If under a flap of skin,. covering the wound surface, transplant a piece of skin, then R. in these cases occurs (Efimov). This fact speaks for the fact that the mechanical obstacle to the growth of the regenerate does not play a role in this phenomenon. The specificity of the skin does not affect the nature of the regenerate. This is evidenced by the experience of Taube, who transplanted the cuff of the red skin of the abdomen in newts onto a limb and, after R., received an ordinary black limb from a place covered with red skin. The same is confirmed by the transplantation of the internal parts of the tail into the skin sleeve of the limb, when y. tail (Bishler). Removing most of the Musculature only affects the speed of the process. It is also necessary to deny the specific influence of the musculature, since the replacement of one region by the transplantation of the musculature for another does not change the nature of the regenerate (Bishler). It has to. recognize that each of the mentioned parts. organ (nerves, skeleton, muscles, skin), taken separately, is not a specific condition for R. V. Parts of the regenerate. The regenerating organ is heterogeneous not only in the sense G that consists of different tissues, it has areas that are extremely different from each other in their properties. If we divide the regenerating organ into two different parts, as is usually done, the blastema and the rest of the regenerate, then their behavior turns out to be sharply different. When the blastema is removed, the latter is again formed by the remaining parts, the same happens when a part of the organ that does not contain the blastema is transplanted into some other area of ​​\u200b\u200bthe body. At the same time, even very small pieces of the transplanted area can develop the corresponding organ (Fig. 15). The situation is different when transplanting another part of the regenerated blastema. At the same time, it was found that until a certain age, about two weeks, blastemas, when transplanted, do not develop further and resolve (Shaksel). Blastems in the experiments of de Giorgi, transplanted onto the back in the ■513

Figure 15. Results of ■transplantation of ter-

Nei limbs in place of the tail. (According to Gie-no and Pons.) grow up to 30 days, although they took root and increased somewhat, but did not experience differentiation. What kind of conditions are important here, it is difficult to say, in any case, the conclusion from these facts can only be that for the presence of R., a connection between the blastema and the rest of the regenerate is necessary. A number of authors tried to find out which part of the regenerating organ is specific, distinguishing one organ from another. Especially much attention has been paid to the question of whether the material of the blastema is specific. Relevant studies were limited to transplantation of blastemas from one organ to another in order to find out whether this would change the specificity of the organ formed from the blastema. Blastema transplants have been performed on various animal species. At the same time, it was found that the regenerate, transplanted to a certain age, develops in accordance with tail on me- rrpRW w G that pbnyaoto rm-one hundred shoulders and fragments with that OOL region of the orta of the territory in front of which he transplanted. That. these experiments speak for the nonspecificity of blastema. However, all studies carried out so far are not convincing enough. Milosevic (MiloseVІc), when transplanting young regenerates of the hind limb to the place of the forelimb, received in a number of cases a formation in a new place of the forelimb, i.e., development in accordance with the place of transplantation. However, these data are not conclusive due to the lack of a reliable criterion that the resulting organ actually originates from the transplant tissue, and not from the regenerating forelimb itself. In the experiment of Guienot and Schotte, where the blastema of a limb, being transplanted onto the tail, gave rise to a tail, the authors themselves doubt the origin of the material of the organ: Finally, Weiss transplanted tail regenerates into the region of the forelimb and in three cases developed the limb. However, even in these experiments one cannot be sure whether R is due to the graft tissues. Thus, the question of the possibility of changing the path of development of the regenerate in amphibians, and at the same time the question of the specificity of the blastema, remains open. A similar situation holds for the lower animals. The experiments of Gebhardt, who in two cases received the formation of a head from the regeneration bud of the tail of a planarian, can be interpreted as the result of participation in the regeneration of the tissues of the head region, where the transplant was performed. All of the above applies only to young regenerates, since all authors agree that newly formed tissues taken at a relatively late age already differ in specificity. Despite the lack of evidence of transplantation experiments in young regenerates, most authors consider not the blastema to be specific, but only the rest of the organ. The presence of mitogenetic radiation in the regenerate made it possible to express the idea that the radiation of some parts of the regenerate may influence others, especially mitogenetic rays arising during tissue resorption, on the multiplication of blastema cells (Blyakher and Bromley). For the present however value of mitogenetic radiation at R. cannot be considered established. Still, there is no doubt that by influencing the regenerate with some kind of genetic rays, it is possible to cause an acceleration of the process (Blyakher, Vorontsova, Irihimovich, Liozner). The same authors showed the presence of stimulation of regenerative processes in cases where the wound surfaces have the ability to influence each other (for example, with a triangular cutout of the tail section). G. The processes occurring in the body during regeneration and c and and. R. is a process that depends not only on the state of this organ, but also on the whole organism. Therefore, the processes occurring in the latter can have a decisive influence on the regeneration process. In the experiments of Getch, the amputation of the head of a hydra did not lead to R. in the case when the hydra had a kidney. Then only regulatory processes took place, as a result of which the head of the enlarged kidney takes the place of the head of the polyp. If one head of a two-headed planaria is amputated, then the latter does not regenerate (Stein-man). A change in the localization of the regenerating organ in relation to the body may not, however, have an effect on the nature of regeneration. Kurz (Kurz) transplanted the amputated limb on the back, and here the normal limb regenerated. Weiss swapped the fore and hind limbs of the newt, and again the R. of the transplanted limbs led to the development of the organ that would have formed if they had been left in place. The same takes place when transplanting a section of the tail or the front of the head. That. one or another place in the development of the process is not specific for R. The influence of the organism on R. of its parts can affect not only the very possibility of R., but also the nature of the regenerate, its shape, position and course of the process. An example of such an impact can be, for example, the significance of a function for the regeneration process, when the use of an organ greatly affects the regenerate. The value of other parts of the body for R. of this area is revealed in experiments with endocrine glands; removal of the endocrine glands or exposure to their hormones can affect the course of R. There is no doubt that a number of processes occurring in the body affect the regeneration process. Of these, we can mention cases of simultaneous presence in the body of several regenerative processes. Whether there will be at the same time stimulation or braking R. - depends on the specific conditions which are expressed in the size of these damages, their arrangement, etc. (Zeleny). The influence of the connections existing in the organism on R. is manifested in experiments on cutting out small sections from the body of hydras or planarians. In this case, a polarity perversion can occur, when identical organs form on both sides of the regenerate (the formation of animals with two heads or two tails, depending on the area from which the regenerating site was cut).

D. Environment. That R. can proceed only in the appropriate environment is quite obvious. With a composition of the medium that has a harmful effect on tissues, the regeneration process is of course impossible. For R.'s normal flow, the environment must meet a number of conditions. These include, first of all, a certain oxygen content (Loeb). Further R. is possible only within certain temperature limits. Ideal for amphibians is equal to 28 °, above and below this temperature R. slows down, at 10 ° it completely stops. According to the study of Moore (Moore), the speed of R., depending on t °, obeys the law of van't Hoff. For aquatic animals, the composition of the surrounding fluid is of great importance. R. is possible only at a certain concentration of sea water (Loeb, Steinman). The best R. is observed in diluted sea water. Some salts (potassium, magnesium) are also necessary for the presence of regenerative pro-

Fig. 16. Tail-pieces (Loeb) > OTHER eye-cuts of Pianaria go- nocephala with its regeneration. Popov received when exposed to 1 ; glad significant stimulation b- no impact; regeneration process - A ~ B ?? 5 / eE M B pi e 5 t ^ G sa "V03 Action U I on the plan - in ^ action 10 minutes" R ii and POLYPOV solution with tannin + KJ-through 4mi MgCl 2, KJ s glyceride - day; With-the same through 7nom, tannin and other things-days. (According to Korshelt.) with effects (Figure 16). Sti. Substances that lower the surface tension of the medium also have a stimulating effect on regeneration, E. The nature of the damage. The regeneration process depends not only on the area where the amputation is performed, but also on the nature of the damage. With a small cut on the wall of the animal's body, rapid healing can occur with an almost complete absence of tissue neoplasm. When applying, however, in the same place several incisions that interfere with such healing, on - ^ .„ „ g vrmnmn Fig "17" Development of a hydrant from ^xyiicici lyrici of the lateral region of the polyp Corymor-pronounced repha palma under the influence of radial generation incisions: I-cuts; 2, 3, ttpttarr r pr 4-gradual development of the hydran process, in re-ta. (From Child.) As a result, a whole organ develops (for example, the head of an animal; Loeb, Child) (Fig. 17). The atypical course of R. may depend on the nature of the damage. So, with a bifurcation of the amputated organ, double formations occur. The position of the regenerate may also depend on how the amputation is performed, since the long axis of the resulting regenerate is usually perpendicular to the plane of the amputation. Theories of R. The phenomenon of R. has been known for a very long time. A number of scientists of ancient times can find indications of acquaintance with this phenomenon. However, the systematic experiments devoted to the study of R. were already set closer to the present. Reaumur (Reaumure) studied regeneration in cancer, attributing this phenomenon to the presence of additional "rudiments of organs (1721). Tremblay's data on hydras dating back to 1744 are known, which established a clearly pronounced regenerative ability of this animal. The middle and end of the 18th century include a number of studies according to R. These include the data of Bonnet and Spallanzani (Bonnet, Spallanzani). These studies capture not only lower, but also a number of higher animals (vertebrates). In the next years R.'s studying proceeded very slowly. Only at the end of the 19th century did an intensified study of regenerative phenomena begin, covering the most diverse types of animals. This study is characterized not only by its systematic and detailed nature, but also by the fact that researchers have already penetrated much deeper into the essence of the phenomenon of R. Researchers of the late 19th century. much attention is paid to elucidating the connections of the regeneration process, its necessary conditions, and on this material they build the corresponding theories of R. The fundamental approach of these authors to the study of the process was substantiated in the works of V. Roux and can be called the causal-analytical method of research. Its characteristic features are the mechanistic and formal nature of the analysis of phenomena; the moments leading to the emergence of the phenomenon under study are taken not in the process of development, but as immovable. By decomposing the process into separate components, the main component is singled out, which is taken as the initial one, and the phenomenon itself is considered as the result of the impact of various conditions on this basis. On the other hand, since the direction of the process is considered in isolation from its driving forces, then a separate factor responsible for the direction of the process is also singled out on the basis of a formal analysis. That. the sources of development and direction of the phenomenon are external in relation to the individual components of the process. Since the source of development acts as an external one in relation to the other components of the process, the question of what causes the development of the very source of development is inevitable. If any factor is singled out as the latter, then the question of the source of development of this new factor will again arise. Proceeding thus, we must either come to the divine first impulse or renounce the final resolution of the question. All the incorrectness of the causal-analytical method clearly follows from this description of it. The generality of the method does not, however, prevent R.'s researchers from disagreeing with each other on a number of essential issues, thus forming. various camps. Part of the scientists, closer to Roux himself, stood on a point of view that bore a preformist character. The very development of the regenerate is caused, in their opinion, by the irritation caused by amputation. The direction of R. is determined mainly under the influence of reserve hereditary rudiments, which are thus. represent the properties of the future organ and, getting into various parts of the regenerate during further reproduction of cells, induce them to the corresponding development. Most of these researchers simultaneously held the point of view that each tissue of a regenerating organ is formed at the expense of a similar tissue of the remainder of the organ, and their development proceeds to a certain extent independently of each other (the theory of P. "Teil fur Teil"). The preformist, causal-analytical theory of R. must be resolutely rejected. It excludes the idea of ​​the actual process of neoformation, interpreting the phenomenon as the realization of what already existed. Preformist ideas proceed from the assumption that we have in a latent form in the form of hereditary rudiments the preformed structure of the future organ. All this assumption is extremely artificial and is in conflict with modern data. Also, a number of observations disproved the position on the independent development of individual tissues of the regenerate at the expense of the corresponding tissues of the stump. Along with this view, another one arises, the justification of which belongs to Driesch and is in sharp contradiction with the first view. Driesch accepts that the regenerate is not preformed in the regenerating parts, otherwise one would have to assume the presence in each part of innumerable mechanisms corresponding to various developmental possibilities. This conclusion is based on the fact that at various levels of amputation, a normal organ arises, therefore, the same part of the regenerate can develop one formation in one case, and another formation in another. Driesch therefore believes that the regenerate is homogeneous in terms of the regenerative capacity of its individual sections and is devoid of any structure that predetermines future development. The differences between the parts of the future organ are not due to differences in the parts of the regenerate, but to the unequal position of them as a whole (regenerate). Hence Driesch's well-known proposition that the fate of a part depends on its position as a whole. The nature or essence of the differences under consideration is determined, however, not by the situation as a whole, but by some non-material factor called by Driesch entelechy. The aspirations of entelechy are aimed at ensuring that the regenerate develops in the direction necessary for the organism. Driesch comes to the recognition of the non-materiality of the factor that determines the direction of R. by excluding other possible explanations, in his opinion, which are reduced to grossly mechanistic ideas. So. arr., according to Driesch, the picture of the regeneration process is drawn in this form. The moment that causes R. is an indefinable closer violation of the body, resulting from amputation and prompting the body to correct the deficiency. R.'s direction is determined by entelechy, which acts expediently, and therefore depends on the final goal of R., that is, the form of the organ that should be formed. ■ The undoubted idealism of Driesch's concepts does not prevent him from remaining a mechanist. It is easy to see that the method used by Driesch to explain phenomena is the same Roux's causal-analytical method, but this time serving to substantiate vitalistic concepts. Driesch's source of development is also external in relation to the developing object, and development is analyzed only in its formal conditionality. As a result of such an analysis, a purely formal statement about the dependence of differences on the position of the part is obtained. Driesch thinks to understand the essence of the process by highlighting a special factor that influences the nature of the phenomenon - entelechy. If in this part of Driesch's constructions he cannot be accused of a lack of at least formal logic, then the same cannot be said about his reasoning about the activity of entelechy. Here the bias and far-fetchedness of Driesch's theory immediately catches the eye. Having smashed the crudely mechanistic view and believing that this excludes any materialistic understanding of the process, Driesch tries to explain the phenomenon of R. by introducing an immaterial principle. Such a position, however, essentially means only the appearance of an explanation, but in fact it is a rejection of the latter; the place of actual study is occupied by the activity of the imagination. -Already very soon, a number of studies showed the unsuitability of Driesch's theory for explaining R. and its direct contradiction with the observed facts. It has been shown that the regeneration process occurs whether or not it is expedient. Transplanted organs regenerate in an unusual place for them, giving formations there that violate the harmony of the body, which cannot therefore. be considered the goal towards which the regeneration process is directed. The evoking of the regeneration process in an unusual place by adducting a nerve shows that it is not the absence of an organ that is the driving moment of R., and the direction of the latter is connected not with an expedient, non-material beginning, but with the completely material properties of the regenerating area. In addition, since the resulting organ is never quite similar to the previously existing one, and sometimes it is completely different from it, the desire to “restore the lost” can be challenged at all. The insufficiency of Driesch's vitalistic constructions prompted researchers to look for a different solution to the regeneration problem. At the same time, the old preformist doctrine was also sufficiently compromised. This explains the attempts io-g structures of theories of R., which would go in a different direction and would be devoid of the shortcomings of the old ones. The most developed theories in this respect are those of Guienot and Weiss and date back to the 1920s. From epigeneticists, these researchers borrow the idea of ​​homogeneity in terms of the potencies of the regenerate material, at the same time they believe that the development of the blastema is determined by the tissues located directly behind the regenerate. Thus, according to these authors, the direction of development is introduced by a factor external to the regenerate; on the other hand, such a factor turns out to be the remnant of an amputated organ, that is, a very specific object of study, and not a mystical otherworldly factor, as is the case with Driesch. The possibility of such a construction is achieved by the fact that two different parts of the regenerate are opposed to each other: the newly formed tissues and the old ones lying behind them. The former are declared on the basis of transplantation experiments to be devoid of specificity until a certain time. On the contrary, the latter is characteristic of old fabrics. The conclusion from this is that the development of newly formed tissues is accomplished under the influence of old ones; the former do not have an independent direction of regeneration embedded in them, it is induced in them by the underlying tissues that impart their structure to the blastema. This basic initial position receives one or another development and shades, depending on which view the author adheres to. Guieno, who is closer to preformism, opposes the old epigenetic point of view that R.'s direction depends on the organism as a whole with the idea that an organism is a mosaic of autonomous regions, each of which is capable of forming only a specific organ peculiar to it. Such isolated parts of the organism Hyeno calls "regeneration territories". Assuming that the specificity of development is communicated to the regenerate by the underlying tissues, Guienot tries to continue the analysis and find out which part of these tissues can be considered responsible for the direction of R. Since none of the tissues used in the experiment (nerves, muscles, skeleton, skin) turns out to be specific condition of R., then Guienot comes to the conclusion that either this property must be attributed by the method of excluding connective tissue or connected with the territory as a whole. Any of these statements would be premature from his point of view. Weiss, who is more inclined towards epigenetic concepts, formulates his views differently. He also accepts that the newly formed tissues do not contain any tendency to develop one or another organ, they are "nullipotent", unorganized. Any organization, according to Weiss, can arise only under the influence of already organized material. The last are the parts lying behind the regenerate. The influence of organized material on unorganized material does not occur in such a way that its parts influence independently of each other - organized material influences as a whole, it carries a "field". What the regeneration field is essentially, Weiss does not explain; he points only to certain purely formal properties of it, for example. the possibility of merging two "fields" into one, etc. Each area of ​​the body has its own specific "field", so. According to Weiss, the organism is also a mosaic of "fields". However, this mosaic is the result of embryonic development, the result of the division of the once homogeneous embryo into independent parts, or the division of the general “field” of the embryo into several “fields”. That resolution of the regeneration problem, which is given by Gieno and Weiss, cannot in any way be considered satisfactory. Their mistake lies again in the mechanistic nature of the analysis, in the application of the causal-analytical method. The direction of R. is investigated by them not in connection with the driving forces of the regeneration process, but independently of them; only its formal conditionality is studied. Only a formal analysis allows us to draw from the position that the regenerate is non-specific to a certain stage, the conclusion about the introduction of R.'s direction from the outside, under the influence of the underlying tissues. This is achieved by artificially opposing the parts of the regenerating site, exposing them as external to each other. - It is easy to show that the theories under consideration do not resolve the contradictions between the epigenetic and preformist points of view. The idea of ​​the source of development as a part of the organism, external to the object under consideration, is not directly discredited only as long as we are dealing with P phenomena. But if, logically continuing the course of the authors’ reasoning, we raise the question of what determines development at the initial moment of ontogenesis when there is still an undifferentiated egg, then we must inevitably either recognize the presence of some factor external to it or return to the insoluble contradictions of the former preformist point of view. The difficulties that arise before the theory under consideration are naturally reflected in the fact that we still do not get an explanation for the regeneration process. Hyeno completely refuses to judge the essence of the action of the territory, while the “field” of Weiss, despite all the author’s attempts to deprive him of mystical character, still remains no clearer concept than Driesch’s entelechy, and undoubtedly points to Weiss’s vitalistic tendencies. The theories mentioned so far are purely morphological. approach to the object under study. The theory fiziol represents opposite to this point of view. Child gradients. Child puts differences in fiziol at the forefront of his theory. properties of different areas of the body. The latter can be detected in various ways: by studying oxygen consumption, sensitivity to various reagents, etc. Child attributes the resulting quantitative differences to be of decisive importance in terms of developmental influence. The degree of physiol. activity causes the appearance of a particular formation. Child t. o. replaces one-sidedness morfol. no less one-sided physiological, purely quantitative point of view. This resolution of the question is, of course, also unsatisfactory. Since with R. it is a question of the formation of qualitatively different organs, a purely quantitative view is condemned "to sterility. Indeed, the connection between the presence of this or that gradient and the emergence of a particular organ remains unclear for Child. Further, there are differences in the physiological activity of various areas, according to Child, its source is a certain area of ​​the body, from which comes the necessary influence, which has an energy character. The emergence of such a "dominant" area is the result of the reaction of protoplasm to an external factor in relation to it. The idea under consideration does not essentially answer the inevitable question why the reaction is of this particular nature.Child's theory bears the same stamp of mechanism and a formal approach to the phenomenon as previously analyzed, and therefore cannot give a correct and consistent idea of ​​the process.Thus, all the R.'s theories we have considered cannot be recognized correspond to reality., He and are not able to identify the driving forces of the phenomenon, the moments that determine it, giving a wrong idea about the process. Due to the fact that R. researchers were guided by an erroneous method, extracted 18 they have to interpret the results quite differently than they do. We have to deny the determining role of various factors, "identified as a result of the study. R., and recognize these factors as only the conditions of the process. However, this view cannot be limited; since the selection of these conditions in most works proceeded from the wrong point of view, the conclusions of the authors On the other hand, it is clear that it is impossible to settle down on the position of conditionalism and it is necessary to identify those defining relationships that underlie the regeneration process. only one can give a deep knowledge of the phenomenon At the present time we do not yet have such a theory, however, it can be pointed out that its construction involves consideration of the process in its self-motion, not a formal analysis, but the discovery of the real driving forces of the process. Liozner. human regeneration, as well as in general with all living beings, there are two types. A. Normological, or physio logical, R. takes place in the daily normal life of a person and manifests itself in the constantly ongoing replacement of obsolete tissue elements with newly formed cells. It is observed to some extent in all tissues, in particular in the bone marrow, regenerative reproduction and maturation of erythrocytes are constantly going on, compensating for dying red blood cells; in the integumentary epithelium, in Krom, there is a continuous detachment of keratinizing cells, all the time they are compensated by the multiplying cells of the deep layers of the epithelial cover.-B. Pathological R. occurs as a result of a stalemate. death of tissue elements. R.'s process in the last sort cases, as a matter of fact, is not a stalemate. process; Pat. R. differs from normological R. not in its essence, but in its scale and other features associated with the nature of the previous loss of tissue elements. Since the death of tissue elements as a result of various stalemate. factors is something very different from fiziol. obsolete cells in both quantitative and qualitative terms, hence the stalemate. R. quantitatively and qualitatively differs from normological R. Manifestations stalemate. The rivers are most often connected with inflammatory process and from the last they are inseparable by a sharp border; it is often impossible to strictly delimit what belongs to inflammation and what to R.; in particular, the proliferative factor in the inflammatory response is very difficult to separate from the regenerative cell multiplication. One way or another, any inflammation implies subsequent R., although R., as indicated, may not be associated with inflammation. The course of R.'s process varies depending on the nature of the damage and the method of death of tissue elements. If there was an action of a factor that caused, along with damage, an inflammatory reaction of the tissue, then usually R.'s manifestations begin only after the acute period of inflammation, accompanied by a significant disruption of tissue vital activity, subsides. If tissue necrosis occurs due to damage or as a result of a developed inflammatory process, then R. precedes or is combined with the processes of resorption of dead material; the latter often occur with the participation of an inflammatory reaction. In contrast, if cell death is a consequence of degenerative and their atrophic changes, then R. goes along with these necrobiotic processes and is not accompanied by inflammation; in particular, in the liver, in the kidneys, along with the degeneration of part of the parenchymal elements, one can see the phenomena of regenerative reproduction of better preserved cells; with atrophy of one lobe of the liver from pressure , eg. echinococcus, in the other lobe, cells multiply, often completely covering the ongoing loss of hepatic tissue. R. is based on the multiplication of cells corresponding to their normal division; while indirect, karyokinetic (mitotic) cell division is of primary importance, while direct, amitotic division is rarely observed. In addition to pictures of normal karyokinesis with stalemate. The river can take place a stalemate. forms of mitotic division in the form of abortive, asymmetric, multipolar mitoses, etc. (see. Mitosis). As a result of regenerative reproduction of cells, young, immature cellular elements are formed, which later mature, differentiate, reaching the degree of maturity that is characteristic of normal cells of this type. If R.'s process concerns separate cells, then morphologically it is expressed in emergence among fabric of separate young cellular forms. If it is a matter of reviving a more or less extensive tissue territory, then as a result of regenerative cell reproduction, an immature, indifferent tissue of the germinal type is formed; this tissue, consisting at first only of young cells and vessels, later differentiates and matures. The period of the immature state of the regenerating tissue, depending on the rate of the process and on various external conditions, can have a different duration. In some cases, the entire process of the formation of a new tissue proceeds gradually, little by little, and new tissue elements are not formed and mature at the same time; under conditions such as happens with growths of the interstitial tissue of parenchymal organs (liver, kidneys, heart muscle), depending on the atrophy of the parenchyma, the period of the immature state of the tissue is morphologically indeterminate. On the contrary, in other cases, namely, when the tissue of a given region undergoes vigorous regenerative growth, a morphologically obvious immature tissue is formed, further maturing at a given period of time; the most demonstrative in this sense is the growth of granulation tissue. In most regenerative processes, the rule of maintaining the specific productivity of tissues is carried out, that is, the fact that the cells that multiply during R. form the tissue from which this reproduction comes: the reproduction of the epithelium gives rise to epithelial tissue, the reproduction of connective tissue elements forms the connective tissue. However, on the basis of data on R. in lower vertebrates, and in relation to humans - data relating to stalemate. R., inflammatory growths and tumors, one has to admit exceptions to this rule in the form of the possibility of education in some cases from the multiplying and, so to speak, embryonic epithelium of mesenchymal tissues (connective tissue, muscles, blood vessels), and from the connective tissue - development muscle elements, vessels, blood elements. In addition, during regeneration in certain tissue groups (epithelium, connective tissue formations), a change in the type of tissue may occur, that is, what is called metaplasia (cm.). It is conventionally customary to distinguish R. complete and incomplete. Complete R., or restitution" (restitut-io ad integrum) is such a revival of tissues, in which a new tissue is formed in place of the dead tissue, corresponding to the one that was lost, for example, restoration of muscle tissue in violation of the integrity of the muscle, restoration of the epithelial cover during the healing of a skin wound.Incomplete R., or substitution, includes those cases when the defect is not filled with a tissue similar to the one that was here before, but is replaced by an overgrowth of connective tissue, which gradually turns into scar tissue; R. is also referred to as healing by scarring.It often happens that there are signs of R. of specific elements of this tissue (for example, in a damaged muscle, the formation of “muscle kidneys” from muscle fibers), however, R. does not go to the end and the defect is replaced mainly connective tissue Incomplete R. occurs when b. or m. organization of damaged tissue (see below) or due to the presence of certain unfavorable conditions, the reproduction of specific elements of a given tissue does not occur at all or it goes too slowly; under such conditions, the proliferation of connective tissue predominates. It should be noted that, in reality, complete R. in the sense of restoration of a tissue that is no different from the previous, normal tissue of a given place, is never observed. The newly formed fabric corresponding to morfol. and func. sense of the former fabric, yet always differs from it to some extent. These differences are sometimes small (underdevelopment of individual elements, some irregularity of tissue architecture); in other cases they are more significant; for example, the formation of the same tissue, but of a simplified type (the so-called hypotype) or the development of tissue in a smaller volume. This also includes cases of superregeneration, manifested in lower animals in the formation of extra organs, limbs (see above), and in humans in the so-called. overproduction of fabrics; the latter lies in the fact that the regenerative growth of the tissue goes beyond the boundaries of the defect and gives an excess of tissue. This is very common, eg. with bone injuries, when excessively newly formed bone tissue appears in the form of thickenings, outgrowths, sometimes very significant; at R. in epithelial covers and ferruterous bodies when the multiplying, the epithelium forms very considerable growths approaching manifestations of tumoral growth, for example. atypical growths of the epithelium in R. ulcers and wounds of the skin and mucous membranes, regenerative adenomas in the liver and kidneys in diseases of these organs, accompanied by the death of part of their parenchyma. In most cases, such an overgrown tissue is devoid of func. values; sometimes (in the bones) it is. further subjected to decline by resorption. R.'s conditions at the person are very various and difficult. Among them, of great importance are those very numerous factors with which the reactive abilities of the organism in general are associated; this includes the hereditary-constitutional characteristics of the organism, age, the state of the blood and circulation, the state of nutrition and metabolism, the function of the endocrine and autonomic systems, as well as the living and working conditions of the individual. Depending on the settings of these factors, R. can go at one pace or another, with one degree or another of perfection; at different individuals at damage of identical type R. of a fabric can proceed normergically, hyperergically, anergically or at all to be absent. Local conditions from the area where R. occurs are also important for R.: the state of blood circulation, lymph circulation in it; the absence or presence of inflammation, especially suppuration. It goes without saying that the formation of new cells can occur only with sufficient! blood supply of nutrient material; Further, the reproduction and maturation of cells cannot occur in tissues that are in a state of sharp inflammation. The nature of the regenerating tissue in terms of the degree of its organization and specific differentiation, as well as other features of the structure and existence of the tissue, is very significant for R.. The higher the development of the tissue, the more complex its organization and differentiation, the more special its function, the less the tissue is capable of R.; and, conversely, the less complex the tissue is built and differentiated, the more regenerative manifestations are characteristic of it. This rule of inverse proportionality between the ability of tissues to R. and the degree of their organization is not, however, absolute; except for the degree of differentiation, other biol always matter. and structural features of the tissue; e.g. cartilage cells are much less capable of R. than more complexly organized epithelial cells. In general, however, it can be noted that poorly differentiated cells of the connective tissue, cells of the integumentary epithelium have a great ability to R., while the possibility of regenerative reproduction of such highly differentiated elements as the nerve cells of the brain and spinal cord, as the muscle fibers of the heart, has not yet been proven and doubtful. In the middle are cells of the secretory epithelium of the glandular organs and fibers of voluntary muscles, which are characteristic of R., but far from being as perfect as the connective tissue and the integumentary epithelium. The fact that regenerative reproduction is more characteristic of less mature and developed cells is also manifested in the fact that in everything. which tissue regeneration comes from those zones in which less mature elements are preserved (in the integumentary epithelium from the basal or germinal layer, in the glands - from the nasal parts of the excretory ducts, in the bone - from the endosteum and periosteum); these zones It is customary to call proliferation centers or growth centers.Regeneration of individual tissues.R. of blood, for example, after blood loss, occurs in such a way that first, by diffusion and osmosis through the vascular wall, blood plasma is restored, after which new, red and white blood cells, to-rye are reborn in the bone marrow and in the lymphadenoid tissue (see. Hematopoiesis).---R. blood vessels is important because it accompanies R. of any tissue. There are two types of new vessel formation.-A. Most often, budding of old vessels takes place, a cut consists in the fact that in the wall of a small vessel there is swelling of the endothelial cell and karyokinetic division of its nucleus; a kidney that bulges outwards (formation of the so-called angioblast) is formed, later on, with continued division of the endothelial nuclei, it is extended into a long cord; in the latter, a gap appears in the direction from the old vessel to the periphery, due to which the initially massive strand turns into a tube that begins to let blood through. The new vascular branches thus formed are connected to each other, which gives the formation of vascular loops.-B-. The second type of neovascularization is called autogenous vascular development. It is based on the formation of vessels directly in the tissue without connection with the former vessels; gaps appear directly among the cells, into which capillaries open and blood is poured out, and adjacent cells receive all the signs of endothelial elements. This mode, similar to embryonic vascular development, can be observed in granulation tissue, in tumors, and apparently in organizing thrombi. Depending on the conditions of blood circulation, the newly formed vessels, which at first had the character of capillaries, can later acquire the character of arteries and veins; the formation of other elements of the vascular wall, in particular smooth muscle fibers, in such cases is due to the reproduction and differentiation of the endothelium. The formation of new connective tissue takes place as a regenerative manifestation in case of damage to the connective tissue itself and, in addition, as an expression of incomplete R. (see above) of a wide variety of other tissues (muscular, nervous, etc.). In addition, neoplasm of connective tissue is observed in a wide variety of pathologies. processes: with the so-called. productive inflammations, with the disappearance of parenchymal elements in organs due to their atrophy, degeneration and necrosis, with wound healing, with processes organizations(mass media encapsulation(cm.). Under all these conditions, the formation of a young, immature granulation tissue(see), undergoing maturation to the degree of mature connective tissue. -R. adipose tissue originates from the nucleated remnants of the protoplasm of fat cells or by converting ordinary connective tissue cells into fat cells. In either case, rounded lipoblast cells are first formed, the protoplasm to-rykh is made of a mass of small fat droplets; Later on, these droplets merge into one large drop, pushing the nucleus to the periphery of the cell. R. bone tissue in case of bone damage is based on the reproduction of osteoblasts of the endosteum and the cambial layer of the periosteum, to-rye, together with the newly formed vessels, form osteoblastic granulation tissue. With bone fractures(see) this osteoblastic tissue forms the so-called. provisional (preliminary) callus. In the future, a dense, homogeneous substance appears between the osteoblasts, due to which the newly formed tissue acquires the property of an osteoid tissue; the latter, petrifying, turns into bone tissue. In fractures, this coincides with the formation of definitive (final) callus. With the func. the load establishes a certain architecture of the newly formed bone tissue, which is accompanied by the resorption of excess parts and the formation of new ones (bone restructuring). Cartilage tissue is capable of R. to a relatively weak degree, and cartilage cells do not participate in regenerative manifestations. With minor damage to the cartilage, the cells of the deep layer of the perichondrium, called chondroblasts, multiply; together with newly formed vessels, these cells form chondroblastic granulation tissue. Between the cells of the latter, the main substance of the cartilage is produced; part of the cells “atrophies, disappears, the other part turns into cartilage cells. Large cartilage defects heal with scarring.-R. muscle tissue, see Muscles. Epithelial tissue, especially the integumentary epithelium of the skin, mucous membranes, serous integuments, is highly capable of R. With defects in the stratified squamous epithelium of the skin and mucous membranes, a new epithelial tissue is formed, which is the product of karyokinetic cell division of the germ layer of the preserved epithelium. The resulting young epithelial cells move towards the defect and cover it first with one layer of low cells; further at proceeding reproduction of these cells the multilayered cover is formed, in Krom there is a maturation and a differentiation of cells, corresponding to structure of a usual multilayer flat epithelium. On the mucous membranes covered with a cylindrical epithelium, defects are replaced by advancing epithelial cells, which are the products of reproduction of cells of the remaining glands (in the intestine - Liberkynrvy, in the uterus - uterine glands); here, in the same way, the defect is first covered with low, immature cells, which later mature, become high, cylindrical. At R. of a mucous membrane of a uterus and intestines from such epithelial cover at the proceeding reproduction of its cells tubular glands are formed. The flat epithelial cover of the serous membranes (peritoneum, pleura, pericardium) is restored through the karyokinetic division of surviving cells; at the same time, at first, the newly formed cells are larger and cubic in shape, and then flatten. ■Y57 In relation to R. of glandular organs, it is necessary to distinguish, on the one hand, the death and revival of only the glandular epithelium while maintaining the basic structure of the organ, and on the other hand, damage with subsequent R. of the entire tissue of the organ as a whole. R. of the epithelial parenchyma of the glandular organs after its partial death due to necrosis and rebirth occurs very completely. With various degenerations and necrosis, for example. epithelium of the liver, kidneys, preserved cells undergo karyokinetic (less often direct) division, due to which the lost elements are replaced by equivalent glandular cells. The revival of parts of the glandular organs is generally more difficult and in general is very rarely perfect. In some glands, for example. in the thyroid gland and in the lacrimal glands, the formation of offspring from the preserved glandular tissue and the formation of new glandular cells are sometimes observed. In other organs, the revival is much weaker; often the processes of hypertrophy and hyperplasia of the remaining epithelial elements predominate over it. In particular, in the liver, when its tissue dies, reproduction occurs and at the same time an increase in the volume of liver cells occurs only within the remaining lobules; on the section of such a liver with the naked eye in the appropriate places, a larger pattern of the structure of the lobules is often noticeable. In general, such processes of reproduction and increase in the volume of cells in the preserved hepatic tissue can reach a very high degree; there are observations indicating that with the gradual removal of 2 / 3 parts of the liver, the remaining third of it can give an increase in volume, covering the above loss. In contrast, the formation of "new hepatic tissue as a whole, i.e., new lobules with their system of capillaries, etc., is never observed. Very often there is a neoplasm of the bile ducts, giving numerous new branches; at the ends of the latter, the cells often undergo an increase in volume and begin to resemble liver cells, but they do not develop beyond this.In the kidneys, when their tissue dies, for example, in the formation of a heart attack, new renal tissue is not formed at all, only sometimes the formation of small offspring from the tubules is observed. an increase in the volume of the glomeruli and tubules in the preserved parts of the kidney.When R. epithelial tissue often undergoes a significant restructuring of it, i.e., a change in the shape and relationships of structural parts.Sometimes metaplasia occurs; often overproduction of tissue occurs in the form of atypical growths of the epithelium (see. higher). In the nervous tissue, R. to a very different extent concerns the actual nerve elements and neuroglia. The revival of dead nerve cells in the formed central nervous system of a person apparently does not occur at all; only occasionally were described - not quite convincing pictures of the nuclear fission of these cells, as it were, beginning to divide. Sympathetic ganglion cells. nervous system in a young organism can multiply, but this is very rare. All loss of matter in the central nervous system heals by filling the defect with a growing tissue of neuroglia, which is highly capable of regenerative manifestations, especially the so-called. mesoglia. In addition, large defects in the brain tissue can be filled with connective tissue growing from the meninges or from the circumference of blood vessels. R. peripheral nerves, see. nerve fibers, regeneration of nerve fibers. A. Abrikosov. Lit.: Astrakhan V., Materials for the study of patterns in the process of regeneration, Moscow, 1929; Davydov K., Restitution in nemerteans, Proceedings of the Special Zoop. cab. And Sevastopol biol. station, Academy of Sciences, series 2, no. 1, 1915; Leb Zh., Organism as a whole, Moscow-Leningrad, 1920; Korschelt E., Regeneration and Transplantation, Band I, Berlin, 1927; Morgan T., Regeneration, New York, 1901; Scha-xel J., Untersuchungentiber die Formbildung der Tiere, Band I - Auff assungen und Erscheinungen der Regeneration, Arb. aus dem Gebiete der experiment. Biologie, Heft 1, 1921.