Events in Regeneration
Regeneration process in higher animals like newts and salamanders involves a series of complicated histological transformations. Needham (1952) recognized the following events in
the regeneration of amputated limbs.
(i) Wound Healing:Amputation or injury to an organ results in exposure of the inierior tissues to the outside. Some cells in the injured region get destroyed. There may be bleeding at the injured surface. The blood soon clots and blocks {urther flow of blood to the outside. Then the epidermal cells proliferate and migrate from all sides towards the centre of the wound . Thus the epithelium forms a complete covering
over the injured tissues underneath the blood clot. The time needed for such a healing process depends on the size of the wound, size of the regenerating animals and external temperature
(ii) Demolition and Defence:The next event is the destruction and removal of the darnaged tissues and the {oreign elements such as germs. These are removed by autolysis and phagocytosis by the blood cells. This is favoured by the increased blood supply to this area
(iii) De-differentiation:De-differentiation refers to the reversion of differentiated cells to the embryonic totipotent condition. Cells f rom the adjacent epidermis, muscles, nerves, cartilages, connective tissue, etc. undergo dedifferentiation. The intercellular matrix of bone and cartilage becomes dissolved and the osteoblasts and chondroblasts are set free. They dedifferentiate into totipotent cells. Similar dedifferentiation occurs in muscle cells, connective tissue fibres and nerve cells. All these cells revert to embryonic totipotent state.
(iv) Blastema Fomation:Next step is the formation of the blastema or regeneration bud. This is due to the accumulation of de-differentiated cells under the epithelial covering of the wound. As more and more cells aggregate below the epidermis, it becomes pushed out and a conical projection appears. This bud like region consisting of an outer cap of epidermis
and central core of de-differentiated cells is called blastema or regeneration bud.
(v) Growth:The blastema then grows in size. This is caused by the mitotic division of the blastema cells.
(vi) Re-differentiation :After attaining sufficient size, the blastema passes into reditferentiation stage. The bone cells, cartilage cells, muscle cells, nerve cells and connective tissue cells are again re differentiated. They give rise to the bones, muscles, nerves and connective tissues of the organ which is to be regenerated . A blastema undergoes re-differentiation exactly like a limb-bud in the embryo
Physiological changes involved in regeneration
Great deal of physiological changes occur during regeneration. Some of the notable changes are:During regeneration two periods with different types of metabolism have been noted
1.Catabolic Phase-During this phase
a.the proteolytic activity increases to a considerable extent. This is mainly due to the increase in the activity of the enzymes, cathepsin and dipeptidases. As a result, the amount ol free amino acids increases. This occurs during the destructive phase of regeneration. The activity of proteolytic enzymes help in destroying the damaged tissues.
b. Anaerobic glycolysis is accelerated during regeneration. It results in an accumulation of lactic acid in the tissues, thus lowering the pH in the blastema.
c. The Respiratory Quotient falls abruptly immediately after regeneration. This may be due to incomplete oxidation in the tissues.
2.Anabolic Phase-During this phase
a.Increase in oxidation
b..RQ Increases
c.Level of lactic acid in the tissues decreases and pH pHreturns to normal
d. Large amounts of RNAs are synthesized.
e. The size of the nucleolus increases in the regenerating cells
Factors affecting regeneration.
(i) Temperature : The rate of regeneration is controlled, to a certain extent, by temperature. lf the temperature is very low, the regeneration process either does not occur or it becomes much slower.The increase in temperature upto a certain limit accelerates the regeneration. But a too high temperature is lethal for all regeneration processes. ln Planaria larva, for example, regeneration is impossible at 3oC. Regeneration is most rapid at 29.70C. A temperature of 320C or above is proved to be lethal for the regeneration process and the animal as a whole.
(ii) Oxygen supply :The amount of oxygen supply affects the rate of regeneration. ln hydroid coionies, the length of regeneration blastema increases with increased concentration of oxygen.
(iii) X-rays: X-rays inhibit regeneration, because they are known to suppress mitotic activity of cells. The inhibiting effect of X-rays depends upon the amount of irradiation administered. Once treated with X-rays, an animal retains the damaging effect for a long time, sometimes until the death of the animal.
(iv) Nervous system : Nervous system has a definite role in controlling the regeneration process. ln amphibians, the early stages of regeneration cannot proceed normally in the absence of an adequate nerve supply to the region of the wound. lf the nerves supplying the leg or the arm of a newt are destroyed simultaneously with the amputation of the limb, the regeneration of a new limb is arrested. The infiuence of nervous system on regerieration has also been demonstrated in annelids. ln earthworms, for example if lhe nerve cord is excised some distance away from the level at which an amputation is made, no regeneration will occur at the cut surface. It has been postulated that the cut ends of the nerves release some regeneration promoting chemical substances called trophic agents. These trophic agents stimulate the regeneration process.
(v)Growth facters:Glial growth factor,transferring ,Epidermal growth factor,Ffibroblast growth factors.
(vi)Proteins and chemicals:Transferrin,retinoucacid etc
(viiAge:The power of regeneration usually diminishes with increasing age.It is well known fact that bone fractures and wound heal much more rapidly in child than in an elderly person.
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