What is regeneration, can it occur in people. Regeneration. Regeneration can be physiological, reparative and pathological Complete regeneration
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Definition of regeneration
Regeneration (from Lat. ge-again, generare - reproduce, create) - restoration (replacement) of the structural elements of cells and tissues to replace those lost. In biological terms, regeneration is the most important universal property of all living matter, developed during evolution and inherent in all living organisms (the universal law of self-renewal of the animal and plant world). All cells, tissues and organs are characterized by regeneration.
Etiology and mechanisms of development. The reasons for regeneration are the hereditary properties of living matter itself, capable of self-development, self-motion, self-regulation and adaptive variability. These qualities determine the relationship and interconnection of living organisms with the external environment of their existence. In this case, the death and decay of structural elements in the body play a trigger role and are the driving force of the regeneration process.
.The mechanisms of regeneration are complex. The development of the restoration process is associated with the self-reproduction (reproduction) of nucleic acids specific to each organism and the directed synthesis of proteins in the genetic apparatus of all living beings (from viruses and phages to higher mammals).
The basis of the life activity of any organism and its regeneration are metabolic processes in all structural elements, which are characterized by wear and spontaneous decay (death) of the material substrate (dissimilation) with the release of energy necessary for life, the release of final metabolic products and specific self-reproduction (assimilation) of living matter using chemical inorganic and organic substances.
The biochemical basis of regeneration is the breakdown and restoration of the molecular composition, structural and spatial organization and functions characteristic of each tissue and organ. For the development of the regenerative process in cells and tissues, an important role is played by shifts in metabolism (hypoxia, increased glycolysis, acidosis, etc.) in the damaged organ, stimulating regenerative processes (lowering the surface tension of cell membranes, their migration), and the inclusion of cells in the mitotic cycle. Molecular fragments formed during cell damage (nucleotides, enzymes, products of incomplete breakdown of proteins, fats and carbohydrates, other biologically active compounds), along with a stimulating effect, can be reused to build complex structures according to the principle of multiple turnover of cell substances for partial material support of regenerative processes.
Reasons for regeneration is damage to organs and tissues, i.e. trigger mechanism. Without damage there is no regeneration.
Regeneration conditions. The speed and perfection of regeneration depends on the state of the animal’s body, feeding and housing conditions, age, etc. Regeneration stimulants are heat, ultraviolet rays, necroharmones, etc.
Regulatory mechanisms of regeneration. Intracellular and cellular regeneration are regulated by certain regulatory mechanisms: nervous, humoral, functional and immunological. Nervous mechanisms of regeneration are determined by the trophic function of the nervous system, regulation of blood and lymph circulation. Humoral regulatory mechanisms are associated with the activity of organs and cells of the endocrine system (hormones, mediators, etc.), with intracellular regulators (cyclic adenosine-3,5-monophosphate and guanosine-3,5-monophosphate) and the activity of reparative enzymes. Intracellular regulators are also tissue-specific inhibitors - mitosekeylons (from the Greek chaiaino - slow down, weaken) and their antagonists - anticeplons, which have a corresponding effect on the synthesis of DNA, RNA and specific proteins. The most important mechanism and stimulating force of regeneration are the physiological needs for renewal or replacement of lost tissue or part of an organ, or a functional stimulus. Immunological mechanisms for regulating the regenerative process are determined by the patterns of maintaining immunological homeostasis and the activity of immunocompetent cells.
The course of regeneration is largely influenced by the age of the animal. In young animals it proceeds faster and more completely than in old ones, and wound healing through complete recovery is often observed. Nutritional and metabolic diseases, lack of nutrients, vitamins and microelements, hard work, various diseases and exhaustion of animals reduce the rate of wound healing and contribute to the development of long-term non-healing wounds and ulcers. With a lack of vitamin C and under the influence of ionizing radiation, paraplastic substances are poorly formed, and there is a tendency to hemorrhage. Disorders of blood and lymph circulation complicate the course of regeneration and create conditions for incomplete regeneration. The state of the nervous, hormonal and immune systems plays an important role in the quality of regeneration.
Regeneration classification
The organization and encapsulation of the process, which relate to the protective-adaptive reactions of the body, usually develops as a result of pathological processes such as necrosis, inflammation of any etiology, etc. The organization is characterized by the growth of connective tissue at the site of dead parenchyma and is usually observed with small sizes of necrosis. Encapsulation develops in cases of significant necrosis. They are separated from healthy tissue by a capsule of connective tissue, which reduces the process of intoxication of the body. Often these processes are observed in tuberculosis, glanders, brucellosis and other infectious diseases.
Depending on the completeness of the correspondence of newly formed cells and tissues to the lost ones, 3 forms of regeneration are distinguished:
- Complete.
- Incomplete.
- Excessive.
Complete regeneration it is called such when the multiplied tissue completely corresponds to the lost one. Typically this type of regeneration is observed with minor damage.
Incomplete regeneration This is called when connective tissue grows in place of the lost tissue. As a rule, it develops with extensive and deep lesions. In practice, this type of regeneration most often develops.
Excessive regeneration when the multiplied tissue is larger in volume than the lost tissue. This is usually observed with prolonged irritation (tuberculosis, actinomycosis, glanders, etc.).
Physiological regeneration is called the replacement of tissue elements lost as a result of physiological reasons (epidermis, cells, blood, epithelial cover of mucous membranes, etc.). When the replacement of some elements by others occurs gradually without any special morphological and functional changes.
Regenerative regeneration is called the replacement of lost parts of organs and tissues lost from excessive causes, while in contrast to physiological hypertrophy there are sharp morphological deviations.
Most often in practice we have to deal with incomplete reparative regeneration, when connective tissue grows in place of dead parenchymal elements.
Morphogenesis and classification. According to the developmental mechanism, restoration of structure and function can occur at the molecular, subcellular, cellular, tissue and organ levels. The oldest in evolutionary terms and the most universal form of regeneration, characteristic of all living organisms without exception, is intracellular regeneration. It includes a biochemical renewal of the molecular composition of cells (molecular, or biochemical, regeneration), nuclear apparatus and cytoplasmic organelles (intraorganoid regeneration), an increase in the number and size of the nuclear apparatus and cytoplasmic organelles (mitochondria, ribosomes, plastic complex, etc.).
According to etiology and mechanism of development There are physiological, reparative regeneration, regenerative hypertrophy and pathological regeneration.
Physiological regeneration- restoration of elements of cells and tissues as a result of their natural death. A living organism continuously renews itself throughout its life in the process of growth and development due to the destruction of old and reproduction of new structures. Plastic processes that occur in tissues during their normal functioning and ensure their constant self-renewal are called physiological regeneration. Its result is the complete restoration of the lost structural elements, i.e. restitution (from the Latin restitutio - restoration). Physiological regeneration proceeds intensively in all organs and tissues. The integumentary epithelium of the skin and mucous membranes of the digestive, respiratory and genitourinary tracts are constantly renewed; glandular epithelium of the liver, kidneys, pancreas, other endocrine and exocrine organs; cells of serous and synovial membranes, as well as other organs. The intensity and qualitative characteristics of physiological regeneration are influenced by the animal’s age, physiological state, and external conditions (feeding, housing, use).
Reparative (from Latin reparatio - compensation), or restorative, regeneration - restoration of the structural elements of cells and tissues as a result of their pathological death. It is based on physiological patterns, but unlike physiological regeneration, it occurs with varying intensity and is characterized by the replacement of parts of the body damaged by the influence of various pathogenic factors with new subcellular, cellular and tissue structures. These reparative processes are observed during injuries, in dystrophic and necrotic organs and tissues. Depending on the degree of damage to the organ, the outcome of reparative regeneration can be not only complete restoration, or restitution (from the Latin restitutio - restoration), of a damaged or lost part of an organ or tissue (as in physiological regeneration), wound healing by primary intention, but also incomplete restoration or replacement, for example, the formation of connective tissue to replace the lost one (wound healing by secondary intention with the formation of dense scar tissue).
Regenerative hypertrophy (from the Greek huper - many, trophe - nutrition)- replacement of the original mass of an organ to replace the lost mass by increasing the remaining part of it or other organs without restoring the shape of the organ. The lost or artificially removed part of the organ is not restored, and cell proliferation occurs within the remaining part of the organ. This form of regeneration is characteristic of many internal parenchymal organs: liver, kidneys, spleen, lungs, myocardium, etc. In this case, usually with the replacement of mass, the function of the organ is restored, with the exception of large vessels, the incomplete replacement of the defect of which is not equivalent to the restoration of their function. Internal organs have great regeneration capabilities.
Morphologically, reparative regeneration and regenerative hypertrophy manifest themselves in three forms:
- regenerative hypertrophy - mainly in the form of cellular regeneration (cell hyperplasia). This form of regeneration is characteristic of bone marrow, integumentary tissues, connective tissue, etc.;
- regenerative hypertrophy - predominantly or exclusively in the form of intracellular regeneration (hyperplasia) of specific ultrastructures and an increase in cell size (heart muscle, ganglion cells of the nervous system, etc.);
- mixed form - a combination of cellular and intracellular regeneration (liver, kidneys, lungs, skeletal and smooth muscles, organs of the autonomic nervous and endocrine systems, etc.).
Pathological regeneration This type of regeneration is called in which the normal course of the regeneration process is disrupted and even distorted. The reasons for the atypical course of physiological, reparative regeneration or regenerative hypertrophy are general and local violations of the conditions for the manifestation of the potential of regeneration. These include disorders of innervation, nervous trophism, hormonal, immune and functional regulation of the regenerative process, starvation, infectious and invasive diseases, and radiation injuries.
Pathological regeneration is characterized by a change in the rate (speed) of regeneration or a qualitative distortion of the recovery process. It is expressed in three forms:
- delay in the rate of regeneration with insufficient formation of the regenerative product. Examples of incomplete regeneration include wounds that do not heal for a long time in the focus of chronic inflammation, long-lasting ulcers, incomplete restoration of dystrophically altered parenchymal organs, etc.;
- excess production of defective regenerate (fungal or fungoid ulcer with tumor-like formation of granulation tissue, overproduction of connective tissue with the formation of keloid, excess callus during healing of a bone fracture, etc.);
- the qualitatively perverted nature of regeneration with the emergence of something new in relation to the composition of the regenerate tissues, with the transformation of one type of tissue into another, and sometimes the transition to a qualitatively new pathological process.
Histological and cytological changes during pathological regeneration are characterized by the appearance of pathological forms of mitoses and amitoses (uneven division and divergence of chromosomes with the formation of irregular mitotic figures - asymmetrical, multipolar, abortive mitoses; incomplete and unequal-sized division of nuclei during amitosis, the formation of multinuclear, or giant, cells due to their incomplete fusion or, conversely, dwarf cells, etc.). At the tissue level, a disturbance in the change of phases of proliferation and differentiation, insufficient maturity of cellular and tissue elements, and their morphofunctional inferiority are noted.
Regeneration of tissues and organs
Regeneration can occur in parallel with necrosis and atrophy. In the presence of acute inflammation, regeneration begins only after it subsides. Regeneration is manifested by the multiplication of tissue elements preserved near the site of damage. First, capillaries grow into the damaged area, the vascular system is restored and metabolism is normalized. Damaged tissues are resorbed by micro- and macrophages, which, when disintegrating, are carried away along with waste products and excreted by the kidneys. then, as a result of division, connective tissue cells multiply. Overgrowing capillaries, forming young granulation tissue, nerve fibers, parenchyma and other cells are restored. Young granulation tissue is bright pink, bleeds easily, is rich in young connective tissue cells and capillaries, over time the capillaries become empty, some of the young cells are absorbed, others turn into scar-like dense gray-white tissue.
Blood, lymph, organs of blood and lymph formation have high plastic properties, are in a state of constant physiological regeneration, the mechanisms of which also underlie the reparative regeneration that occurs as a result of blood loss and damage to the organs of hematopoiesis and lymphopoiesis. On the very first day of blood loss, the liquid part of the blood and lymph is restored due to the absorption of tissue fluid into the vessels and the flow of water from the gastrointestinal tract. Blood and lymph cells are then regenerated. Platelets and leukocytes are restored within a few days, red blood cells - a little longer (up to 2-2.5 weeks), later the hemoglobin content levels out. Reparative regeneration of blood and lymph cells during blood loss occurs by enhancing the function of the red bone marrow of the spongy substance of the vertebrae, sternum, ribs and tubular bones, as well as the spleen, lymph nodes and lymphoid follicles of the tonsils, intestines and other organs. Intramedullary (from Latin intra - inside, medulla - bone marrow) hematopoiesis ensures the entry of erythrocytes, granulocytes and platelets into the blood. In addition, during reparative regeneration, the volume of myeloid hematopoiesis also increases due to the conversion of fatty bone marrow into red bone marrow. Extramedullary myeloid hematopoiesis in the liver, spleen, lymph nodes, kidneys and other organs occurs with large or prolonged blood loss, pernicious anemia of infectious, toxic or nutritional-metabolic origin. Bone marrow can recover even with major damage.
Pathological regeneration blood and lymph cells with a sharp inhibition or perversion of hemo- and lymphopoiesis is observed in severe damage to the blood and lymph-forming organs associated with radiation sickness, leukemia, congenital and acquired immunodeficiencies, infectious and hypoplastic anemia. A pathognomonic sign of pathological regeneration is the appearance in the blood and lymph of immature, functionally inferior atypical forms of cells.
Spleen and lymph nodes when damaged, they are restored according to the type of regenerative hypertrophy.
Blood and lymphatic capillaries have high regenerative properties even with major damage. Their new formation occurs by budding or autogenously.
Physiological regeneration fibrous connective tissue occurs through the reproduction of lymphocyte-like mesenchymal cells derived from a common stem cell, poorly differentiated young fibroblasts (from the Latin fibro - fiber, blastano - form), as well as myofibroblasts, mast cells (labrocytes), pericytes and microvascular endothelial cells. From young cells, mature fibroblasts (collagen- and elastoblasts) actively synthesize collagen and elastin differentiate. Fibroblasts first synthesize the main substance of connective tissue (glycosoaminoglycans), tropocollagen and proelastin, and then in the intercellular space they form delicate reticular (argyrophilic), collagen and elastic fibers. During the restructuring and involution of connective tissue, fibroblasts and macrophages play an active role.
Reparative regeneration connective tissue damage occurs not only when it is damaged, but also when other tissues are incompletely regenerated and during wound healing. In this case, the fibrous tissue eventually turns into dense, coarse fibrous scar tissue.
Regeneration bone tissue occurs as a result of the proliferation of osteogenic cells - osteoblasts in the periosteum and endosteum. Reparative regeneration in case of bone fracture is determined by the nature of the fracture, the state of bone fragments, periosteum and blood circulation in the area of damage. There are primary and secondary bone fusions. Primary bone fusion is observed when bone fragments are immobile and is characterized by the ingrowth of osteoblasts, fibroblasts and capillaries into the area of the defect and bruise.
Secondary bone fusions are often observed in complex fractures, mobility of fragments and unfavorable regeneration conditions (local circulatory disorders, extensive damage to the periosteum, etc.). With this type of reparative regeneration, the fusion of bone fragments occurs more slowly, through the stage of formation of cartilaginous tissue (preliminary osteochondral callus), which subsequently undergoes ossification.
Pathological regeneration of bone tissue is associated with general and local disorders of the recovery process, long-term circulatory disorders, death of bone fragments, inflammation and suppuration of wounds. Excessive and improper new formation of bone tissue leads to bone deformation, the appearance of bone outgrowths (osteophytes and exostoses), and the predominant formation of fibrous and cartilaginous tissue due to insufficient differentiation of bone tissue. In such cases, with the mobility of bone fragments, the surrounding tissue takes on the appearance of ligaments, and a false joint is formed.
Regeneration cartilage tissue occurs due to chondroblasts of the perichondrium, which synthesize the main substance of cartilage - chondrin and turn into mature cartilage cells - chondrocytes. Complete restoration of cartilage is observed with minor damage. Most often, incomplete restoration of cartilage tissue occurs, its replacement with a connective tissue scar.
Regeneration adipose tissue occurs due to cambial fat cells - lipoblasts and an increase in the volume of lipocytes with the accumulation of fat, as well as due to the proliferation of undifferentiated connective tissue cells and their transformation as lipids accumulate in the cytoplasm into the so-called signet ring cells - lipocytes. Fat cells form lobules surrounded by a connective tissue stroma with vessels and nerve elements.
Regeneration muscle tissue It happens both physiologically and after fasting, white muscle disease, myoglobinuria, toxicosis, bedsores, infectious diseases associated with the development of atrophic, dystrophic and necrotic processes.
Skeletal striated muscle tissue has high regenerative properties while maintaining the sarcolemma. The cambial cellular elements located under the sarcolemma - myoblasts - multiply and form a multinuclear symplast, in which myofibrils are synthesized and striated muscle fibers are differentiated. When the integrity of the muscle fiber is damaged, newly formed multinuclear symplasts in the form of muscle buds grow towards each other and, under favorable conditions (small defect, absence of scar tissue), restore the integrity of the muscle fiber.
Cardiac striated muscle tissue regenerates according to the type of regenerative hypertrophy. In intact or dystrophically altered myocardiocytes, structure and function are restored due to organelle hyperplasia and fiber hypertrophy. With direct necrosis, myocardial infarction and heart defects, incomplete restoration of muscle tissue can be observed with the formation of a connective tissue scar and with regenerative myocardial hypertrophy in the remaining parts of the heart.
Regeneration of nervous tissue. During life, ganglion cells of the brain and spinal cord are intensively renewed at the molecular and subcellular levels, but do not multiply. When they are destroyed, intracellular compensatory regeneration (hyperplasia of organelles) of the remaining cells occurs. Compensatory-adaptive processes in nervous tissue include the discovery of multinucleolar, binucleate and hypertrophied nerve cells in various diseases accompanied by degenerative processes, while maintaining the general structure of the nervous tissue. The cellular form of regeneration is characteristic of neuroglia. Dead glial cells and small defects of the brain and spinal cord, autonomic ganglia are replaced by multiplying cells of neuroglia and connective tissue with the formation of glial nodules and scars. Nerve cells of the autonomic nervous system are restored through organelle hyperplasia, and the possibility of their reproduction cannot be excluded.
Peripheral nerves completely regenerate provided that the connection between the central segment of the nerve fiber and the neuron is maintained and the cut ends of the nerve diverge slightly.
If nerve regeneration is impaired (significant divergence of parts of the cut nerve, disordered blood and lymph circulation, the presence of inflammatory exudate), a connective tissue scar is formed with disordered branching of the axial cylinders of the central segment of the nerve fiber. In the stump of a limb after amputation, excessive growth of nerve and connective tissue elements can lead to the formation of a so-called amputation neuroma.
Regeneration of epithelial tissue. The integumentary epithelium is one of the tissues with a high biological potential for self-healing. Physiological regeneration of the stratified squamous epithelium of the skin occurs constantly due to the proliferation of cells of the germinal (cambial) malpighian layer. When the epidermis and stroma of the skin are damaged, the cells of the germ layer at the edges of the wound multiply, creep onto the restored membrane and stroma of the organ and cover the defect (wound healing under the scab and by primary intention). However, the newly formed epithelium loses the ability to completely differentiate the layers characteristic of the epidermis, covers the defect with a thinner layer and does not form skin derivatives: sebaceous and sweat glands, hair (incomplete regeneration).
The integumentary epithelium of the mucous membranes of the digestive, respiratory tract and genitourinary tract (stratified squamous non-keratinizing, transitional, single-layer prismatic and multi-row ciliated) is restored by the proliferation of young undifferentiated cells of the crypts and excretory ducts of the glands. As they grow and mature, they become specialized cells of the mucous membranes and their glands.
Incomplete regeneration of the esophagus, stomach, intestines, gland ducts and other tubular and cavitary organs with the formation of connective tissue scars can cause narrowing (stenosis) and their expansion, the appearance of unilateral protrusions (diverticula), adhesions (synechia), incomplete or complete fusion (obliteration) of organs (cavities of the cardiac sac, pleural, peritoneal, articular cavities, synovial bursae, etc.).
Regeneration of the liver, kidneys, lungs, pancreas, and other endocrine glands occurs at the molecular, subcellular and cellular levels based on the patterns inherent in physiological regeneration, with great intensity. With focal irreversible damage (necrosis) in parenchymal organs, as well as with partial resection, the mass of the organ can be restored according to the type of regenerative hypertrophy. At the same time, in the preserved part of the organ, a multiplication and increase in the volume of cellular and tissue elements is observed, and scar tissue forms at the site of the defect (incomplete recovery).
Pathological regeneration of parenchymal organs is observed with various long-term, often repeated injuries (disorders of blood circulation and innervation, exposure to toxic toxic substances, infections). It is characterized by atypical regeneration of epithelial and connective tissues, structural restructuring and deformation of the organ, and the development of cirrhosis (cirrhosis of the liver, pancreas, nephrocirrhosis, pneumocirrhosis).
2. Hypertrophy and hyperplasia
Definition of hypertrophy and hyperplasia
Hypertrophy(from Greek hyper - a lot, trophe - food) and hyperplasia(from the Greek plasso - form) are called compensatory-adaptive processes that are causally determined by an increased functional stimulus, manifested by an increase in the number and size of structural elements and an increase in their function. Structural and functional changes during hypertrophy and hyperplasia are associated with an increase in metabolic rate.
Hypertrophy- increase in the volume and mass of an organ, tissue, cells; hyperplasia- an increase in the number of structural elements of an organ, tissues and cells as a result of their reproduction. These processes are based on increased nutrition and increased function of a normally developed organ. If the specialized tissue of an organ increases, it develops true hypertrophy or hyperplasia. Enlargement of an organ due to connective, fatty tissue or cavity volume is defined as false hypertrophy. Congenital enlargement of an organ associated with the development of a defect (gigantism of the organism, organ or tissue), like age-related growth and development, is not classified as hypertrophy. With cell hypertrophy, hyperplasia of intracellular organelles occurs (nucleoli, nuclei, mitochondria, ribosomes, cytoplasmic reticulum, lamellar complex, lysosomes, etc.), and with hyperplasia of cells, tissues and organs, individual hypertrophied structural elements are noted (for example, polyploid and multinucleated cells). It has been established that in some organs and tissues hypertrophy with intracellular hyperplasia predominates (myocardium, skeletal muscles, nervous tissue), in others - cell hyperplasia (bone marrow, lymph nodes and spleen, connective tissue, integumentary epithelium of the skin and mucous membranes) or a combination of hypertrophy with hyperplasia (liver, kidneys, lungs, etc.).
Classification, causes and morphogenesis of hypertrophy and hyperplasia
Classification, causes and morphogenesis. Based on the origin and mechanism of development, physiological and pathological hypertrophy (hyperplasia) are distinguished. Physiological hypertrophy occurs as a result of increased organ function under the influence of natural causes under physiological conditions. The volume and mass of organs increase in a healthy body with increased work. For example, hypertrophy of the heart and skeletal muscles during strenuous physical work (horses, donkeys, oxen) and in sports animals; hypertrophy of the mammary gland (up to 70 kg or more) of highly productive dairy cows as a result of milking; other organs also enlarge. Physiological hypertrophy of the uterus and mammary glands is observed during pregnancy and lactation. Physiological hyperplasia of lymphoid tissue occurs as a result of antigenic stimulation of the body by normal microflora.
For physiological hypertrophy characterized by increased activity of genetically determined mechanisms of neurohormonal regulation, increased intensity of respiration, nutrition and metabolism, morphofunctional changes in the relevant organs and tissues.
Pathological hypertrophy occurs as a result of increased work of an organ or tissue under the influence of excessive loads under pathological conditions. The development of pathological hypertrophy is characterized by the formation of a new level of neuro-hormonal regulation and metabolic processes in the diseased body. Depending on the causes and mechanism of development, working (compensatory), vicarious (replacement), hormonal, vacate hypertrophy and hypertrophic growth are distinguished.
Working (compensatory) hypertrophy develops as a result of increased work of the organ during illnesses and injuries. The defects that arise in the tissues create an increased functional load for the surviving structures of the organ, which determines the occurrence and development of hypertrophy and hyperplasia. As a compensatory phenomenon, hypertrophy of the heart muscle is observed with congenital and acquired defects (for example, hypertrophy of the left half of the heart with insufficiency or stenosis of the bicuspid valve, semilunar valves of the aorta), hypertrophy of the right heart with difficulties in the pulmonary circulation (with insufficiency or stenosis of the tricuspid valve, semilunar valves pulmonary artery, for chronic pneumonia, emphysema and other pneumopathy); hypertrophy of the liver and kidneys with increased protein feeding; hypertrophy of the bladder with prostatitis and narrowing of the urethra; hypertrophic processes in the gastrointestinal tract, etc.
Vicarious (replacement) hypertrophy develops in the remaining part of the organ with irreversible damage to any part of it or in one of the paired organs (kidneys, lungs, adrenal glands, etc.) with unilateral atrophy and atrophic cirrhosis, as well as after surgical removal. Vicarious hypertrophy is one of the forms of working or regenerative hypertrophy, in the development of which increased functional load on the remaining organ, metabolic, reflex and hormonal factors play an important role.
Hormonal hypertrophy and hyperplasia occur when the function of endocrine organs is disrupted, for example, with ovarian dysfunction, glandular cystic endometrial hyperplasia can develop; During castration, fatty tissue hypertrophies and signs of obesity appear. Pituitary adenoma is accompanied by an increase in the volume of the limbs and protruding parts of the skeleton, in particular the facial part of the skull, acromegaly (from the Greek akros - extreme, protruding, megalos - large). In pathological terms, hormonal hypertrophy and hyperplasia are of a correlative nature (correlative hypertrophy and hyperplasia), acting as compensatory reactions to significant changes in hormonal homeostasis, in the alignment of which neurohumoral factors play an important role (neurohumoral hypertrophy).
Vacuum hypertrophy (from the Latin vacuum - empty) is characterized by the growth of connective, fatty or other tissue during atrophy of an organ.
Hypertrophic growth with an increase in tissues and organs occurs as a result of chronic physical or chemical influences, disorders of blood and lymph circulation and inflammation. Long-term stagnation of lymph in the extremities causes excessive pathological growth of connective tissue, the appearance of an elephantine limb. With hypertrophic cirrhosis of the liver, simultaneous proliferation of supporting-trophic connective tissue and specialized glandular epithelium of the organ, etc. is observed.
Macroscopic changes organs and tissues with hypertrophy and hyperplasia are manifested by an increase in their size. The volume and mass of the organ increase, which are determined by appropriate measurements. At the same time, hypertrophied organs are dense, have an intense (full-blooded) color, and in most cases retain their shape, configuration and outline.
Physiological hypertrophy and hyperplasia characterized by a uniform, proportionate increase in the volume of an organ or the number of tissue and cellular elements, proportional development of all its parts in accordance with the action of a general functional stimulus, metabolic and neurohumoral factors.
Pathological hypertrophy and hyperplasia are characterized by a certain unevenness of the process depending on the location, nature and degree of damage to a particular organ as a whole or any part of it (for example, pathological hypertrophy of the heart, depending on the location of the congenital or acquired defect). With cardiac hypertrophy, the walls of the ventricles, trabecular and papillary muscles thicken.
In the heart and other cavitary organs (vessels, stomach, intestines, gall and urinary bladders, uterus), with true hypertrophy, in some cases, thickening of the walls of organs with narrowing of their cavities is noted, in others - simultaneous thickening of the walls of organs and a tonogenic increase in their cavities. with false hypertrophy, the organ increases in volume due to hyperplastic growth of connective or adipose tissue. Parenchymal specialized tissue is in a state of atrophy. In this case, the organ acquires a denser consistency, gray-brown (paler) color, its shape, structure and the relationship of individual parts change.
Hypertrophy does not develop with expansion (dilatation) of the cavitary organs with an increase in volume associated with any disease (dilatation of the heart, stomach, rumen tympany in ruminants, intestinal flatulence). On the contrary, with them, thinning of the walls and an increase in volume due to dilatation of the corresponding cavities are noted .
Microscopic changes in the cells of a hypertrophied or hyperplastic organ are characterized by an increase in the amount of DNA and RNA, specific enzymatic and structural proteins and other biologically active compounds in pre-existing cells (hypertrophy) or reproduction (hyperplasia) with the formation of new cells (mitosis, amitosis). With hypertrophy, the formation of multinucleolar, bi-, tri- and multinucleated giant cells, an increase in the number and volume of mitochondria, endoplasmic reticulum, lamellar complex, lysosomes, cytoskeleton and membrane apparatus of cells are also noted. In this case, the new formation of structural elements in true hypertrophy and hyperplasia occurs synchronously in specialized tissue (in striated and smooth muscles, epithelium, etc.) and in the connective tissue stroma, blood vessels and intramural nervous apparatus. Hypertrophic and hyperplastic changes are established by measuring and comparing the sizes of tissue, cellular and subcellular elements, counting their number per unit area, determining the optical density (extinction) of chemical compounds, the intensity of synthesis and decay of structural elements using modern cytochemical, cytophotometric, radioautographic (labeled isotopes) ) and electron microscopic methods.
The significance and outcome of hypertrophy and hyperplasia are determined by the level and degree of new morphological provision of an increased functional stimulus, the performance of the hypertrophied and hyperplastic organ, the completeness and duration of compensation for impaired functions of organs and tissues. With physiological hypertrophy, organs and tissues, after the cessation of increased loads, can be transformed into a normal morphofunctional state, i.e. this process is reversible. This happens after physiological hypertrophy of the heart and skeletal muscles of working horses, sports dogs, as well as the uterus and mammary gland of females after termination of pregnancy and lactation.
With pathological hypertrophy, full morphological compensation of the impaired function of organs and tissues can ensure enhanced functioning of the organ for a long period, sometimes many years. The duration of the compensation phase and the possibility of returning to normal depend on the state of the hypertrophied or hyperplastic organ, blood and lymph circulation in it, nutrition and metabolism, the level of nervous and hormonal regulation, the degree of elimination of the cause that caused the hypertrophy (hyperplasia) of the organ. If the cause that caused the hypertrophy is active, then the neurohormonal regulation of the hypertrophied organ weakens and becomes depleted, dystrophic, atrophic and sclerotic changes increase in it, and decompensation occurs. For example, a heart defect becomes decompensated due to transverse, passive, or myogenic, expansion of the heart cavity and its morphofunctional insufficiency.
Pathological hypertrophic growths in organs and tissues, caused by prolonged irritating effects of pathogenic factors on them, further weaken and disrupt the functioning of damaged organs.
Regeneration lost organs in animals is a mystery that has troubled scientists since ancient times. Until recently, it was believed that only lower species of living beings were endowed with this magnificent property: a lizard grows back a severed tail, some worms can be cut into small pieces, and each one will grow into a whole worm - there are many examples.
But the evolution of the living world went from lower organisms to increasingly more highly organized ones, so why did this property disappear at some stage? And was it lost?
The Lernaean Hydra, the Gorgon Medusa or our three-headed Serpent Gorynych, whose “self-repairing” heads Ivan tirelessly chopped off, are characters, although mythical, but clearly in a “family relationship” with very real creatures.
These include, for example, newts, a type of tailed amphibian that is rightfully considered one of the most ancient animals on Earth. Their amazing feature is the ability to regenerate - to regrow damaged or lost tails, paws, and jaws.
Moreover, their damaged heart, eye tissue, and spinal cord are restored. For this reason, they are indispensable for laboratory research, and newts are sent into space no less often than dogs and monkeys. Many other creatures have these same properties.
Thus, black and white zebrafish, only 2-3 cm long, tend to regenerate parts of their fins, eyes, and even restore the cells of their own heart, cut out by surgeons during regeneration experiments. This can be said about other types of fish.
Classic examples of regeneration are lizards and tadpoles that regenerate a lost tail; crayfish and crabs growing back their lost claws; snails that can grow new “horns” with eyes; salamanders, which naturally replace an amputated leg; starfish regenerating their severed rays.
By the way, from such a severed ray, like from a cutting, a new animal can develop. But the champion of regeneration was the flatworm, or planaria. If it is cut in half, then the missing head grows on one half of the body, and the tail grows on the other, that is, two completely independent viable individuals are formed.
And perhaps the appearance of a completely unusual, two-headed and two-tailed planaria. This will happen if longitudinal cuts are made at the front and rear ends and do not allow them to grow together. Even 1/280 of the body of this worm will make a new animal!
People watched our smaller brothers for a long time and, to be honest, secretly envied them. And scientists moved from fruitless observations to analysis and tried to identify the laws of this “self-healing” and “self-healing” of animals.
The first to try to bring scientific clarity to this phenomenon was the French naturalist Rene Antoine Reaumur. It was he who introduced into science the term “regeneration” - the restoration of a lost part of the body with its structure (from the Latin ge - “again” and generatio - “emergence”) - and conducted a series of experiments. His work on leg regeneration in cancer was published in 1712. Alas, her colleagues did not pay attention to her, and Reaumur abandoned this research.
Only 28 years later, the Swiss naturalist Abraham Tremblay continued his experiments on regeneration. The creature on which he experimented did not even have its own name at that time. Moreover, scientists did not yet know whether it was an animal or a plant. A hollow stalk with tentacles, with its rear end attached to the glass of an aquarium or to aquatic plants, turned out to be a predator, and a very surprising one at that.
In the researcher's experiments, individual fragments of the small predator's body turned into independent individuals - a phenomenon known until then only in the plant world. And the animal continued to amaze the natural scientist: in place of the longitudinal cuts on the front end of the body made by the scientist, it grew new tentacles, turning into a “many-headed monster,” a miniature mythical hydra, which, according to the ancient Greeks, Hercules fought with.
It is not surprising that the laboratory animal received the same name. But the hydra under study had even more wonderful features than its Lernaean namesake. She grew to a whole even from 1/200 of her one-centimeter body!
Reality surpassed fairy tales! But the facts that are known to every schoolchild today, published in 1743 in the Proceedings of the Royal Society of London, seemed implausible to the scientific world. And then Tremblay was supported by the already authoritative Reaumur, confirming the authenticity of his research.
The “scandalous” topic immediately attracted the attention of many scientists. And soon the list of animals with regenerative abilities turned out to be quite impressive. True, for a long time it was believed that only lower living organisms possess a self-renewal mechanism. Then scientists discovered that birds were able to grow beaks, and young mice and rats were able to grow tails.
Even mammals and humans have tissues with great capabilities in this area - many animals regularly change their fur, the scales of the human epidermis are renewed, cropped hair and shaved beards grow back.
Man is not only an extremely inquisitive creature, but also passionately desires to use any knowledge for his own benefit. Therefore, it is quite understandable that at a certain stage of research into the mysteries of regeneration, the question arose: why does this happen and is it possible to induce regeneration artificially? And why did higher mammals almost lose this ability?
Firstly, experts noted that regeneration is closely related to the age of the animal. The younger it is, the easier and faster the damage is corrected. A tadpole's missing tail easily grows back, but the loss of an old frog's leg makes it disabled.
Scientists studied the physiological differences, and the method used by amphibians for “self-repair” became clear: it turned out that in the early stages of development, the cells of the future creature are immature, and the direction of their development may well change. For example, experiments on frog embryos have shown that when the embryo has only a few hundred cells, part of the tissue destined to become skin can be cut out of it and placed in the brain area. And this tissue... will become part of the brain!
If a similar operation is performed on a more mature embryo, then skin still develops from skin cells - right in the middle of the brain. Therefore, scientists concluded that the fate of these cells is already predetermined. And if for the cells of most higher organisms there is no way back, then the cells of amphibians are able to turn back time and return to the moment when their purpose could have changed.
What is this amazing substance that allows amphibians to “self-heal”? Scientists have discovered that if a newt or salamander loses a leg, then the bone, skin and blood cells in the damaged area of the body lose their distinctive features.
All secondarily “newborn” cells, which are called blastema, begin to rapidly divide. And in accordance with the needs of the body, they become cells of bones, skin, blood... to eventually become a new paw. And if at the moment of “self-repair” you add tretinoinic acid (vitamin A acid), then this boosts the regenerative abilities of frogs so much that they grow three legs instead of the one lost.
For a long time it remained a mystery why the regeneration program was suppressed in warm-blooded animals. There may be several explanations. The first comes down to the fact that warm-blooded animals have slightly different priorities for survival than cold-blooded animals. Scarring of wounds became more important than total regeneration, since it reduced the chances of fatal bleeding when wounded and the introduction of a deadly infection.
But there may be another explanation, much darker - cancer, that is, the rapid restoration of a large area of damaged tissue implies the emergence of identical rapidly dividing cells in a certain place. This is exactly what is observed during the emergence and growth of a malignant tumor. Therefore, scientists believe that it has become vital for the body to destroy rapidly dividing cells, and therefore, the ability to quickly regenerate has been suppressed.
Doctor of Biological Sciences Pyotr Garyaev, Academician of the Russian Academy of Medical and Technical Sciences, states: “It (regeneration) did not disappear, it’s just that higher animals, including humans, turned out to be more protected from external influences and complete regeneration became less necessary.”
To some extent, it has been preserved: wounds and cuts heal, torn skin is restored, hair grows, and the liver partially regenerates. But our severed arm no longer grows back, just as our internal organs do not grow back to replace those that have ceased to function. Nature simply forgot how to do this. Perhaps I need to remind her of this.
As always, His Majesty Chance helped. Immunologist Helen Heber-Katz of Philadelphia once gave her laboratory assistant a routine task: piercing the ears of laboratory mice to attach tags to them. A couple of weeks later, Heber-Katz came to the mice with ready-made tags, but... did not find holes in the ears.
We did it again and got the same result: no hint of a healed wound. The mice's bodies regenerated tissue and cartilage, filling in unnecessary holes. Herber-Katz drew the only correct conclusion from this: in the damaged areas of the ears there is a blastema - the same unspecialized cells as in amphibians.
But mice are mammals, they should not have such abilities. Experiments on the unfortunate rodents continued. Scientists cut off pieces of mice's tails and... got 75 percent regeneration! True, no one even tried to cut off the “patients’” paws for an obvious reason: without cauterization, the mouse would simply die from massive blood loss long before regeneration of the lost limb began (if at all). And cauterization eliminates the appearance of blastema. So it was not possible to find out a complete list of the regenerative abilities of mice. However, we have already learned a lot.
True, there was one “but”. These were not ordinary house mice, but special pets with a damaged immune system. Heber-Katz made the first conclusion from her experiments: regeneration is inherent only in animals with destroyed T-cells - cells of the immune system.
Here's the main problem: amphibians don't have it. This means that the answer to this phenomenon lies precisely in the immune system. Conclusion two: mammals have the same genes necessary for tissue regeneration as amphibians, but T cells do not allow these genes to work.
Conclusion three: organisms originally had two ways of healing from wounds - the immune system and regeneration. But over the course of evolution, the two systems became incompatible with each other - and mammals chose T cells because they were more important, as they are the body's main weapon against tumors.
What is the use of being able to regrow a lost arm if at the same time cancer cells are rapidly developing in the body? It turns out that the immune system, while protecting us from infections and cancer, simultaneously suppresses our ability to “self-repair.”
But is it really impossible to think of anything, because you really want not just rejuvenation, but restoration of the life-supporting functions of the body? And scientists have found, if not a panacea for all ills, then an opportunity to become a little closer to nature, however, thanks not to the blastema, but to stem cells. It turned out that humans have a different principle of regeneration.
For a long time it was known that only two types of our cells can regenerate - blood cells and liver cells. When the embryo of any mammal develops, some cells remain aside from the process of specialization.
These are stem cells. They have the ability to replenish blood or dying liver cells. Bone marrow also contains stem cells that can become muscle tissue, fat, bone or cartilage, depending on what nutrients they are given in the laboratory.
Now scientists had to test experimentally whether there was a chance to “launch” the “instructions” written in the DNA of each of our cells for growing new organs. Experts were convinced that you just need to force the body to “turn on” its ability, and then the process will take care of itself. True, the ability to grow limbs immediately runs into a temporary problem.
What a tiny body can easily do is beyond the power of an adult: the volumes and dimensions are much larger. We can't do like newts: form a very small limb and then grow it. For this, amphibians need only a couple of months; for a person to grow a new leg to normal size, according to the calculations of the English scientist Jeremy Brox, it takes at least 18 years...
But scientists have found a lot of work for stem cells. However, first it is necessary to say how and where they are obtained from. Scientists know that the largest number of stem cells is located in the bone marrow of the pelvis, but in any adult they have already lost their original properties. The most promising resource is considered to be stem cells obtained from umbilical cord blood.
But after birth, researchers can only collect 50 to 120 ml of such blood. From every 1 ml, 1 million cells are released, but only 1% of them are progenitor cells. This personal reserve of the body’s recovery reserve is extremely small and therefore priceless. Therefore, stem cells are obtained from the brain (or other tissues) of embryos - abortive material, no matter how sad it is to talk about it.
They can be isolated, placed in tissue culture, where reproduction begins. These cells can live in culture for more than a year and can be used for any patient. Stem cells can be isolated from umbilical cord blood and from the brain of adults (for example, during neurosurgery).
Or it can be isolated from the brains of recently deceased people, since these cells are resistant (compared to other cells of the nervous tissue); they are preserved when the neurons have already degenerated. Stem cells extracted from other organs, such as the nasopharynx, are not as versatile in their use.
Needless to say, this direction is fantastically promising, but has not yet been fully explored. In medicine, it is necessary to measure seven times, and then recheck for ten years to make sure that the panacea does not lead to any disaster, for example, an immune shift. Oncologists also did not say their strong “yes”. But nevertheless, there have already been successes, although only at the level of laboratory developments and experiments on higher animals.
Let's take dentistry as an example. Japanese scientists have developed a treatment system based on genes that are responsible for the growth of fibroblasts - the very tissues that grow around teeth and hold them. They tested their method on a dog that had previously developed a severe form of periodontal disease.
When all the teeth fell out, the affected areas were treated with a substance that included these same genes and agar-agar, an acidic mixture that provides a nutrient medium for cell reproduction. Six weeks later, the dog's fangs erupted.
The same effect was observed in a monkey with teeth cut down to the base. According to scientists, their method is much cheaper than prosthetics and for the first time allows a huge number of people to literally return their teeth. Especially when you consider that after 40 years of age, a tendency to periodontal disease occurs in 80% of the world's population.
In another series of experiments, the tooth chamber was filled with dentinal filings (playing the role of an inductor) with gingival connective tissue (amphodont) as a reacting material. And the amphodont also turned into dentin. In the near future, English dentists hope to move from successful experiments on mice to further laboratory research. Conservative estimates suggest that stem implants will cost the same as conventional prosthetics in England - between £1,500 and £2,000.
Research has shown that people with kidney failure only need to have 10% of their kidney cells revived to stop being dependent on a dialysis machine.
And research in this direction has been ongoing for many years. How important it is - not to sew it on, but to grow it again, not to sit on pills, but to restore healthy function using the hidden capabilities of the body.
In particular, a way has been found to grow new pancreatic beta cells that produce insulin, which promises millions of diabetics relief from daily injections. And experiments on the possibility of using stem cells in the fight against diabetes are already in the completion phase.
Work is also underway to create products that include regeneration. Ontogeny has developed a growth factor called OP1, which will soon be approved for sale in Europe, the US and Australia. It stimulates the growth of new bone tissue. OP1 will help in the treatment of complex fractures, when the two parts of the broken bone are very misaligned with each other and therefore cannot heal.
Often in such cases the limb is amputated. But OP1 stimulates bone tissue so that it begins to grow and fill the gap between the parts of the broken bone. At the Russian Institute of Traumatology and Orthopedics, researchers obtain stem cells from bone marrow. After 4-6 weeks of propagation in culture, they are transplanted into the joint, where they reconstruct the cartilaginous surfaces.
And a few years ago, a group of English geneticists made a sensational announcement: they were starting work on heart cloning. If the experiment is successful, there will be no need for transplants, which could lead to tissue rejection. But it is unlikely that wave genetics will be limited to the regeneration of only internal organs, and scientists hope that they will learn to “grow” limbs for patients.
Stem cells also have great prospects in the field of gynecology. Unfortunately, many young women today are doomed to infertility: their ovaries have stopped producing eggs.
This often means that the pool of cells from which follicles arise has been exhausted. Therefore, it is necessary to look for mechanisms that replenish them. The first encouraging results in this area have appeared recently.
Scientists are already seeing how to save people who have been given a terrible diagnosis - cirrhosis of the liver. They believe that at some stages of the development of the disease, transplantation of an entire organ can be replaced by the introduction of only stem cells (through the arterial bed, direct punctures, direct cell transplantations into liver tissue). Specialists from the Center for Surgery of the Russian Academy of Medical Sciences have begun a pilot study, and the first results are encouraging.
Ukrainian scientists are conducting very interesting preliminary developments in the field of cardiovascular diseases. Already today they have accumulated experimental evidence that the introduction of stem cells to patients with myocardial infarction or severe ischemia is a promising method of treatment.
The first clinical experiments with stem cell transplantation, which began at the University of Pittsburgh in the USA, also yielded good results in severely ill patients who had suffered an ischemic or hemorrhagic stroke. After cell therapy, their neurological rehabilitation is clearly noticeable.
Unfortunately, the frightening statistics of the number of children with intrauterine brain damage, including cerebral palsy, are very well known. It has already been proven that if such children begin stem cell transplantation (or therapy aimed at stimulating them, i.e., localizing their own, endogenous cells in the affected area), then after the first year of life it is often observed that even with preservation of anatomical Children with brain defects have minimal neurological symptoms.
Effectively developed stem cell transplantation technologies can completely change our lives. But this is the future, and today this field of knowledge does not even have its own name, only options: “cell therapy”, “stem cell transplantation”, “regeneration medicine”, even “tissue engineering” and “organ engineering”.
But it is already possible to list all the possibilities of this new direction. It is not without reason that they say that the 21st century will pass under the sign of biology, and perhaps the experience of regeneration, preserved over millions of years by amphibians and protozoa, will help humanity.
Regeneration, revival, is the process of compensation and restoration of cells, tissues and organs that have died for one reason or another.
It is necessary first of all to distinguish between two types of regeneration: physiological and reparative. Their causes, development mechanism and significance for the body are different.
Physiological regeneration is the replacement of tissue elements lost as a result of natural death. For example, the hematopoietic apparatus compensates for the natural loss of blood elements: red blood cells and granular leukocytes are produced by the bone marrow; lymphocytes are formed in the lymph nodes, in the follicles of the spleen, tonsils, intestines and other organs. The dying cells of the epidermis and mucous membranes are replaced by the multiplying cells of the malpighian (cambial, germinal) layer of these integuments.
Reparative regeneration is the replacement of parts of the body lost under the influence of harmful factors (for example, due to injuries) with newly formed tissue elements.
This process has two varieties:
· complete regeneration, or restitution;
· incomplete regeneration, or substitution.
Complete regeneration—replacement of the defect with tissue corresponding to the lost one. It occurs when the volume of the defect is insignificant, the nervous and vascular apparatus, as well as the germinal layers of the affected tissue and guiding structures (basal membrane, organ stroma) are preserved. Thus, complete regeneration is noted with abrasions (damage to the epidermis without breaking the skin itself), with damage to bones with preservation of the periosteum. In skeletal muscles, this is observed when the sarcolemma is intact (for example, in bedsores, toxicosis). In the newly formed tissue that replaces the defect, it is possible to detect some deviations from the norm, which disappear only after a certain period of time with proper functional load.
Incomplete regeneration is the replacement of a defect with tissue different from the lost one. This is the most common form of regeneration observed in the presence of extensive defects with disruption of neurovascular elements. Typically, the lost part of an organ is replaced by fibrous connective tissue, which over time can undergo hyaline transformation (sclerosis).
Specific tissue elements usually differ from normal ones both in structure and function. For example, with incomplete skin regeneration, the epidermis is much thinner and usually does not form hair, sebaceous, sweat glands or pigment. Pathological regeneration can be expressed in a delay in the rate of recovery, in insufficient formation of regenerate, in a quantitative distortion of the process. In some cases, ulcers that do not heal for a long time may occur.
Pathological deviations of recovery processes also include excessive regeneration (or superregeneration), which is expressed in excessive new tissue formation at the site of damage. For example, when bones heal, calluses form at the site of fractures. With prolonged irritation of the affected area, which prevents its healing, excess granulation tissue grows. Due to the fact that the death of tissue elements is possible both as a result of their natural wear and tear (physiological necrosis) and from the influence of harmful factors (pathological necrosis), a distinction is made between physiological, reparative, and also atypically occurring - pathological regeneration.
Regeneration of individual tissues and organs
The ability to regenerate various tissues in higher organisms is not the same. This process occurs most easily in epithelial tissue, especially in the covering epithelium, then in the epithelium of the excretory ducts of the glands, and more difficult in the glandular epithelium, especially in highly differentiated ones. Unformed connective tissue regenerates easily, but other types of connective tissue, such as bone, are much more difficult to regenerate. Muscle tissue regenerates poorly. Nervous tissue, with the exception of pathways, regenerates poorly, and nerve cells of the central nervous system are not able to regenerate.
Epithelial tissue - flat stratified epithelium of the skin and mucous membranes. Regeneration occurs well, but if there are superficial injuries, separation of the superficial layers of the epithelium occurs, for example, due to abrasions or aphthous processes. The epithelium is reborn from the surviving cells of the germinal, or germinal, layer, in which mitotic and amitotic cell division is observed. As they multiply, the cellular elements move onto the exposed, damaged surface. Initially, the newly formed epidermis does not have complete differentiation. It occurs as the cellular elements mature. With the continued proliferation of cells, a multilayered cover is formed, in which maturation and differentiation of cells occurs, the corresponding structure of the usual multilayered squamous epithelium. Extensive defects are gradually covered by an epithelial cover growing from the surviving cellular islands of the surface of the defect, from the epithelium along the edges of the latter and from the epithelial cells of the excretory ducts of the sebaceous, sweat glands and hair follicles. If skin damage extends not only to the epidermis, but also to the dermis, healing occurs with the formation of a scar. The epithelium over the scar turns out to be thinner than normal, its layers are not sufficiently differentiated. Hair, sweat and sebaceous glands are not restored. On mucous membranes covered with cylindrical epithelium, defects are replaced by advancing epithelial cells, which are the product of the proliferation of cells of the remaining glands (in the intestines - liberkin glands, in the uterus - uterine glands). Here, in the same way, the defect is first covered with low immature cells, which later mature and become tall and cylindrical.
During the regeneration of the mucous membrane of the uterus and intestines, tubular glands are formed from such an epithelial cover with the continued proliferation of its cells, plunging into the depths of the mucous membrane.
The mesothelium of the serous membranes (peritoneum, pleura, pericardium) is restored due to the karyokinetic reproduction of surviving cells. At the same time, at first the newly formed cells are larger in size and cubic in shape, and then they become flattened.
Epithelium of glandular organs
It is necessary to distinguish:
a) death and revival of only the glandular epithelium;
b) damage followed by regeneration of all tissues of a given area of the organ or the entire organ as a whole. Regeneration of the epithelial parenchyma of glandular organs after its partial death occurs completely. In various dystrophies and necrosis, for example of the liver, kidneys, the surviving cells undergo karyokinetic (less often direct) division, due to which the lost elements are replaced by different glandular cells. The revival of parts of the glandular organs as a whole is much more complex and is very rarely perfect. Almost always, the revival occurs poorly, and the processes of hypertrophy often predominate, i.e., an increase in the volume of the remaining epithelial elements. In particular, in the liver, when its tissue dies, the liver cells multiply and simultaneously increase in volume only within the remaining lobules. The formation of new liver tissue as a whole, that is, new lobules with their capillary system and so on, is never observed. Very often, new formation of bile ducts occurs, giving rise to numerous new branches. At the ends of the latter, the cells undergo an increase in volume and begin to resemble liver cells. But their development does not go further than this. However, in the general process of reproduction and increase in volume, cells in the preserved liver tissue can reach large sizes. In the kidneys, when their tissue dies, new kidney tissue is not formed at all. Only sometimes the formation of small offspring from the tubules is observed. At the same time, an increase in the volume of glomeruli in the remaining parts of the kidney may occur.
Fibrous connective tissue regenerates due to the proliferation of fibroblasts and capillary endothelial cells. The youngest connective tissue cells formed in this case - round cell elements - resemble lymphocytes, since they have a round, compact nucleus and a small mass of cytoplasm. As the rate of reproduction slows down, these cells turn into larger elements with a vesicular nucleus and a significant mass of cytoplasm. Due to their similarity to epithelium, connective tissue cells at this stage of development are called epithelioid.
As they mature further, the epithelioid cells acquire a spindle-shaped shape, and thin filaments appear between them, which can only be identified by silvering methods. These fiber-like cells are called fibroblasts, the fibers are called argyrophilic. Subsequently, the fibroblasts are flattened and transformed into fibrocytes, and the fibers are enveloped like a case with an adhesive or elastic substance, turning into collagen and elastic fibers. Over time, the number of fibrocytes decreases, the vessels become partially empty, and the newly formed tissue turns into dense scar tissue.
Bone tissue regenerates depending on the size of the defect, the immobility of bone fragments and the preservation of the periosteum. Bone tissue is restored mainly due to the proliferation of osteoblast cells located in the periosteum and endosteum.
Osteoblasts, filling the defect, form the intercellular substance of bones. At this stage, bone tissue, still devoid of lime, is called osteoid; after impregnation with lime, it acquires all the properties of bone tissue, and mature cellular elements are called osteocytes. Newly formed bone tissue is usually formed in a large volume, which is required to close the defect (preliminary callus, provisional callus). Over time, part of the bone substance is resorbed due to the activity of special osteoclast cells, and the callus acquires a constant size (final callus).
Pathological regeneration of bone tissue is manifested in excessive and abnormal growth of bone in the form of outgrowths, in the transformation of bone tissue into fibrous and cartilaginous tissue. If, during a bone fracture, the bone fragments remain mobile, then their fusion does not occur, the surrounding tissues take on the appearance of ligaments, and false joints are formed.
Cartilage tissue regenerates worse than bone. Recovery occurs through the proliferation of young cartilage cells - chondroblasts, followed by their transformation into typical ones.
Adipose tissue regenerates as a result of the proliferation of surviving young fat cells - lipoblasts and connective tissue cells - fibroblasts.
Blood and lymph
First of all, plasma volume is restored by absorbing water from the tissues and intestines into the vessels. Formed elements with moderate blood loss are formed physiologically due to increased function of the hematopoietic apparatus. With frequent and excessive blood loss, with malignant anemia of toxic and infectious origin, with lesions of the hematopoietic apparatus, when the bone marrow cannot cope with the restoration of blood cells, extramedullary hematopoiesis develops. At the same time, foci appear in the liver, spleen, lymph nodes, kidneys and other organs, resembling bone marrow in structure and cellular composition.
Muscle
Regeneration occurs differently depending on the type of muscle tissue, the nature of the damage and the physiological load. Smooth muscle tissue recovers relatively quickly due to the proliferation of remaining muscle fibers that grow into the site of injury. It is assumed that under the influence of physiological stress, fibrous connective tissue transforms into muscle tissue.
Cross-striated skeletal muscle tissue completely regenerates only if the sarcolemma is preserved. At the same time, inside the tube formed by the sarcolemma, so-called myoblasts are formed from the remaining muscle fibers in the form of a multinuclear syncytial mass. They grow towards each other as the dead muscle substance is absorbed and differentiate into striated fibers. When the sarcolemma is destroyed, a connective tissue scar is formed at the site of damage, connecting the overgrown multinuclear ends of the torn muscle fibers.
Cardiac striated muscle tissue does not regenerate, and a connective tissue scar forms at the site of its damage.
Nervous system
Ganglion cells of the brain and spinal cord do not regenerate from nerve tissue elements. Some scientists allow the restoration of nerve cells of the autonomic nervous system in young animals. Regeneration of nerve trunks is possible only if the cut parts of the nerve are connected with a maximum discrepancy between them of 0.5 cm. The fusion of the ends of the damaged nerve is achieved due to the proliferation of endo- and perineural fibroblasts and peripheral glia (Schwann cells). The proximal ends of the nerve fibers and their sheaths begin to grow. If such growing fibers come into contact with the Schwann sheaths of the peripheral portion of the nerve, the nerve fibers grow into them and grow along the path of the nerve trunk. This growth occurs over a long period of time, over weeks and months, and reaches the nerve endings, whereby nerve function is restored.
Vascular regeneration
Blood vessels such as arteries and veins do not regenerate. Their lumen at the site of injury is closed by a thrombotic mass and overgrown with connective tissue, and blood circulation is restored through collaterals. Capillaries have a high ability to regenerate, which can occur through budding and autogenously. Restoration of capillaries by budding is associated with the proliferation of endothelial cells, which form kidney-shaped outgrowths and cords on the capillary wall, in which a lumen gradually forms. With the autogenous method, gaps appear between the cells, into which blood flows from neighboring capillaries, and the walls of the gaps are gradually overgrown with endothelial cells. Newly formed capillaries connect with surviving vessels and are thus included in the circulatory system.
Adaptive and recovery processes
Important scientific news: biologists from Tufts University (USA) managed to restore the ability to regenerate tail tissue in tadpoles. Such work could be considered ordinary, if not for one circumstance: the result was achieved in a non-trivial way, using optogenetics, which is based on controlling cell activity using light.
The ultimate goal of all such research is to discover the natural mechanisms that control the restoration of body parts and learn how to turn them on in humans. Tadpoles are ideally suited for this task, since at an early stage of development they retain the ability to replace lost limbs, but then abruptly lose it. If you cut off the tail of individuals who have entered the so-called refractory period, they will no longer be able to regrow it.
The internal systems that control regeneration are still present in their body, but for some reason they are stopped. Michael Levin and his colleagues made them work again, essentially turning back physiological time.
It's remarkable how they did it. One group of tailless tadpoles was raised in a container exposed to short flashes of light for two days; the other lived in complete darkness. As a result, the tadpoles of the first group regained full tail tissue, including the structures of the spine, muscles, nerve endings and skin. The second tadpoles were unable to overcome the consequences of amputation, as befits their age.
If it looks like a trick, it's only partly. To understand why this happened, it is necessary to explain the principle underlying the experiment. Indeed, all animals at the same life cycle stage were subjected to identical manipulations. The only thing that distinguished the two groups was the presence or absence of lighting. However, light was not the true cause of the changes that occurred. It served as a remote switch that activated a factor that (in an unclear way) started the regeneration process. Hyperpolarization of transmembrane potentials of cells acted as such a factor; or more simply – bioelectricity.
Optogenetics makes it possible to construct an experiment relatively simply. The mRNA molecules of the light-sensitive protein archerchodopsin were injected into tadpoles. This led to the fact that after some time, “pump proteins” appeared on the surface of ordinary cells located in the thickness of the tissue. When stimulated by light (and only in this case), they induced a current of ions through the membrane, thereby changing its electrical potential.
Essentially, other than light-activated membrane pumps, scientists have offered nothing to help tadpoles. However, just influencing the electrical properties of cells was enough to trigger a complex cascade of regenerative processes in the body. In turn, thanks to optogenetics, inducing these changes from the outside is as easy as shelling pears; you just need to shine the light on the tadpole.
Regeneration remains one of the main mysteries of biology. In 2005, Science magazine listed the following question as one of the 25 most important issues facing science: What Controls Organ Regeneration? Unfortunately, scientists have not yet been able to fully understand why some animals, at any stage of their lives, freely restore lost body parts, while others lose this ability forever. Once upon a time, your body knew how to grow an eye or an arm.
This was a long time ago, at the very beginning of life as an embryo. Specialists are interested in where this knowledge disappears and whether it can be revived again in an adult. Currently, most biologists' searches focus primarily on gene expression or chemical signals. Michael Levin's lab hopes to find the answer to the regeneration mystery in another phenomenon, bioelectricity, and these hopes appear to be well founded.
The fact that electric currents are present in a living organism has been known since Galvani’s experiments. However, few have studied their influence on development as closely as Lewin has. Bioelectricity has long had a chance to become a worthy topic of experimentation, but the molecular revolution in biology in the second half of the twentieth century pushed research interest in this issue to the periphery of science.
Levin, coming from the field of computer modeling and genetics, using the most modern methods that were absent from his predecessors, actually returns this direction to the biological mainstream. At the heart of his enthusiasm is the belief that electricity is a basic physical phenomenon, and evolution could not help but involve it in fundamental processes such as the development of organisms.
By changing the transmembrane potential of the cells, the scientist can instruct the tadpole's tissues to grow an eye in a predetermined area of the body. On the wall of his laboratory hangs a photograph of a six-legged frog. She acquired additional limbs solely as a result of exposure to electrical biocurrents. Unlike neurons, ordinary cells are not capable of firing, but can transmit signals sequentially throughout almost the entire body through gap junctions. If the tail part of a planaria, a tiny worm that can regenerate, is cut off, a request from the area of the cut will go to the head to make sure that it is in place. Block the transmission of this information, and a head will grow instead of a tail.
By manipulating various ion channels that determine the electrical properties of cells, scientists in their experiments produced worms with two heads, two tails, and even an unusual design of worms with four heads. Levin says he was almost always told his ideas wouldn't work. He relied on his intuition, and in most cases it did not fail.
These attempts are still very far from complete knowledge of how to restore a limb in a person. For now, people with disabilities can only rely on improved prostheses. However, a unique laboratory at Tufts University is looking for something even more fundamental: like the genetic code, Levine believes, there must be a bioelectrical code that links membrane voltage gradients and dynamics to anatomical structures.
Having understood it, it will be possible not only to control regeneration, but also to influence the growth of tumors. Levin views them as a consequence of the loss of information about the shape of the body by cells, and the study of cancer is one of the tasks of his laboratory. As is often the case, seemingly different processes can have the same nature.
If the bioelectric code really is behind the construction of various organs of the body, its solution could shed light on two of the most important problems facing humanity.
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Regeneration (in pathology) is the restoration of the integrity of tissues damaged by any disease process or external traumatic influence. Recovery occurs due to neighboring cells, filling the defect with young cells and their subsequent transformation into mature tissue. This form is called reparative (compensatory) regeneration. In this case, two options for regeneration are possible: 1) the loss is compensated by tissue of the same type as the one that died (complete regeneration); 2) the loss is replaced by young connective (granulation) tissue, which turns into scar tissue (incomplete regeneration), which is not regeneration in the proper sense, but the healing of a tissue defect.
Regeneration is preceded by the release of a given area from dead cells by enzymatic melting and absorption into the lymph or blood or by (see). Melting products are one of the stimulators of the proliferation of neighboring cells. In many organs and systems there are areas whose cells are a source of cell proliferation during regeneration. For example, in the skeletal system such a source is the periosteum, the cells of which, when multiplying, first form osteoid tissue, which later turns into bone; in the mucous membranes - cells of deep-lying glands (crypts). Regeneration of blood cells occurs in the bone marrow and outside it in the system and its derivatives (lymph nodes, spleen).
Not all tissues have the ability to regenerate, and not to the same extent. Thus, the muscle cells of the heart are not capable of reproduction, resulting in the formation of mature muscle fibers, therefore any defect in the myocardial muscles is replaced by a scar (in particular, after a heart attack). When brain tissue dies (after hemorrhage, arteriosclerotic softening), the defect is not replaced by nervous tissue, but a tissue is formed.
Sometimes the tissue that appears during regeneration differs in structure from the original (atypical regeneration) or its volume exceeds the volume of dead tissue (hyperregeneration). This course of the regeneration process can lead to tumor growth.
Regeneration (Latin regenerate - revival, restoration) - restoration of the anatomical integrity of an organ or tissue after the death of structural elements.
Under physiological conditions, regeneration processes occur continuously with varying intensity in different organs and tissues, according to the intensity of the aging of the cellular elements of a given organ or tissue and their replacement with newly formed ones. Formed elements of the blood, cells of the integumentary epithelium of the skin, mucous membranes of the gastrointestinal tract, and respiratory tract are continuously replaced. Cyclic processes in the female reproductive system lead to rhythmic rejection and renewal of the endometrium through its regeneration.
All these processes are the physiological prototype of pathological regeneration (it is also called reparative). Features of the development, course and outcome of reparative regeneration are determined by the extent of tissue death and the nature of pathogenic influences. The last circumstance must be especially borne in mind, since the conditions and causes of tissue death are essential for the regeneration process and its outcomes. For example, scars after skin burns have a special character, different from scars of other origins; syphilitic scars are rough, lead to deep retractions and disfigurement of the organ, etc. Unlike physiological regeneration, reparative regeneration covers a wide range of processes leading to compensation of the defect caused by the loss of tissue due to its damage. A distinction is made between complete reparative regeneration - restitution (replacement of the defect with tissue of the same type and the same structure as the dead one) and incomplete reparative regeneration (filling of the defect with tissue that has greater plastic properties than the dead one, i.e. ordinary granulation tissue and connective tissue with further turning it into scar tissue). Thus, in pathology, regeneration often means healing.
The concept of regeneration is also associated with the concept of organization, since both processes are based on the general laws of new tissue formation and the concept of substitution, i.e. displacement and replacement of pre-existing tissue by newly formed tissue (for example, substitution of a blood clot with fibrous tissue).
The degree of completeness of regeneration is determined by two main factors: 1) the regenerative potential of a given tissue; 2) the volume of the defect and the same or heterogeneous species of dead tissue.
The first factor is often associated with the degree of differentiation of a given tissue. However, the very concept of differentiation and the content of this concept are very relative, and comparison of tissues on this basis with the establishment of a quantitative gradation of differentiation in functional and morphological terms is impossible. Along with tissues that have a high regenerative potential (for example, liver tissue, mucous membranes of the gastrointestinal tract, hematopoietic organs, etc.), there are organs with an insignificant potential for regeneration, in which regeneration never ends with complete restoration of lost tissue (for example, myocardium , CNS). Connective tissue, wall elements of the smallest blood and lymphatic vessels, peripheral nerves, reticular tissue and its derivatives have extremely high plasticity. Therefore, plastic irritation, which is trauma in the broad sense of the word (that is, all its forms), first and foremost stimulates the growth of these tissues.
The volume of dead tissue is essential for the completeness of regeneration, and the quantitative limits of tissue loss for each organ, which determine the degree of restoration, are more or less known empirically. It is believed that for the completeness of regeneration, not only volume as a purely quantitative category is important, but also the complex diversity of dead tissues (this especially applies to tissue death caused by toxic-infectious influences). To explain this fact, one should, apparently, turn to the general patterns of stimulation of plastic processes under pathological conditions: the stimulators are the products of tissue death themselves (hypothetical “necrohormones”, “mitogenetic rays”, “trephons”, etc.). Some of them are specific stimulators for cells of a certain type, others are nonspecific, stimulating the most plastic tissues. Nonspecific stimulants include products of the breakdown and vital activity of leukocytes. Their presence during reactive inflammation, which always develops with the death of not only parenchymal elements, but also the vascular stroma, promotes the proliferation of the most plastic elements - connective tissue, i.e., the eventual development of a scar.
There is a general scheme for the sequence of regeneration processes, regardless of the area where it occurs. Under pathological conditions, regeneration processes in the narrow sense of the word and healing processes are of a different nature. This difference is determined by the nature of tissue death and the selective direction of action of the pathogenic factor. Pure forms of regeneration, i.e. restoration of tissue identical to the lost one, are observed in cases where only specific parenchymal elements of an organ die under the influence of pathogenic influence, provided they have a high regenerative potency. An example of this is the regeneration of renal tubular epithelium selectively damaged by toxic exposure; regeneration of the epithelium of the mucous membranes during desquamation; regeneration of lung alveolocytes in desquamative catarrh; regeneration of skin epithelium; regeneration of the endothelium of blood vessels and endocardium, etc. In these cases, the source of regeneration is the remaining cellular elements, the reproduction, maturation and differentiation of which leads to complete replacement of the lost parenchymal elements. When complex structural complexes die, restoration of lost tissue occurs from special areas of the organ, which are unique regeneration centers. In the intestinal mucosa, in the endometrium, such centers are glandular crypts. Their multiplying cells cover the defect first with one layer of undifferentiated cells, from which glands then differentiate and the structure of the mucosa is restored. In the skeletal system, such a regeneration center is the periosteum, in the integumentary squamous epithelium - the Malpighian layer, in the blood system - bone marrow and extramedullary derivatives of reticular tissue.
The general law of regeneration is the law of development, according to which, in the process of neoplasm, young undifferentiated cellular derivatives arise, which subsequently undergo stages of morphological and functional differentiation up to the formation of mature tissue.
The death of areas of an organ consisting of a complex of various tissues causes reactive inflammation (see) along the periphery. This is an adaptive act, since the inflammatory reaction is accompanied by hyperemia and increased tissue metabolism, which promotes the growth of newly formed cells. In addition, inflammatory cellular elements from the group of histophagocytes are plastic material for the formation of connective tissue.
In pathology, anatomical healing is often achieved with the help of granulation tissue (see) - the stage of new formation of a fibrous scar. Granulation tissue develops during almost any reparative regeneration, but the degree of its development and final outcomes vary within very wide limits. Sometimes these are tender areas of fibrous tissue that are difficult to distinguish during microscopic examination, sometimes they are coarse dense strands of hyalinized bradytrophic scar tissue, often subject to calcification (see) and ossification.
In addition to the regenerative potential of a given tissue, the nature of its damage, its volume, general factors are important in the regeneration process. These include the age of the subject, the nature and characteristics of nutrition, and the general reactivity of the body. In case of innervation disorders or vitamin deficiencies, the usual course of reparative regeneration is distorted, which is most often expressed in a slowdown in the regeneration process and sluggishness of cellular reactions. There is also the concept of fibroplastic diathesis as a constitutional feature of the body to respond to various pathogenic irritations with increased formation of fibrous tissue, which is manifested by the formation of keloid (see), adhesive disease. In clinical practice, it is important to take into account general factors to create optimal conditions for the completeness of the regeneration process and healing.
Regeneration is one of the most important adaptive processes that ensure the restoration of health and continuation of life under emergency circumstances created by the disease. However, like any adaptive process, regeneration at a certain stage and along certain paths of development can lose its adaptive significance and itself create new forms of pathology. Disfiguring scars that deform an organ and sharply impair its function (for example, cicatricial transformation of heart valves as a result of endocarditis) often create severe chronic pathology that requires special therapeutic measures. Sometimes the newly formed tissue quantitatively exceeds the volume of the dead tissue (super-regeneration). In addition, in every regenerate there are elements of atypia, the sharp severity of which is a stage of tumor development (see). Regeneration of individual organs and tissues - see the relevant articles on organs and tissues.