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Introduction to histopathology
Introduction to histopathology

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1.7 Wound healing, angiogenesis and tissue regeneration

In many cases cells can divide and regenerate the tissue, restoring it to virtually normal. For example the basal cells of the skin epidermis can divide to cover a scratch or a graze, provided that it does not extend over too great an area. Epidermal cells from hair follicles can contribute to the regeneration, provided that the damage has not gone too deep. In this case there is a balance between regeneration from the epidermis and repair from the dermal layers, the outcome of which will determine whether a scar is formed or not. The process of normal tissue regeneration can be favoured by closing wounds with stitches, or skin grafts. Conversely, if the damage persists or the area of damage is large, fibrosis and scarring prevail.

The ability to regenerate varies greatly between cell types. For example, neuronal cells have a very limited capacity to regenerate (regrow) their axons if they have been severed, and virtually no capacity to replace themselves by cell division. By contrast, hepatocytes have enormous potential for division, which can be seen following removal of a portion of the liver, following surgery; the remaining cells can divide to fully restore the liver to its original size.

In tissue such as skeletal muscle, regeneration is characterised by an increase in the thickness of myofibres (hypertrophy), but without significant increase in their number. The same effect is seen with adipocytes, which increase or decrease in size (i.e. the volume of the lipid-filled vesicle) in response to fasting or over-eating rather than by changes in cell number. In such tissues, the histological appearance can give an indication of tissue damage that has taken place a long time previously.

Angiogenesis is the process by which new blood vessels grow into tissues, forming capillaries.


Under what circumstances would you expect new vessels to grow into tissues?


An increase in the requirements for oxygen or nutrients stimulate angiogenesis. It may be due to an increased metabolic activity of the organ, e.g. in a muscle following training. Regenerating tissues also require a new blood supply, and angiogenesis is frequently a critical requirement for tumour development.

The process of angiogenesis involves new capillaries sprouting from the side of arterioles and extending as blind-ended tubes in the tissue. Eventually they connect up (form anastemoses) with venules to complete a capillary loop (Figure 8). Regenerating tissue often contains numbers of these developing capillaries; in the skin the base of scars has characteristic pink spots, which are the newly sprouting capillaries.

Figure 8 Ischaemic regions of tissue release angiogenic cytokines, including VEGF (vascular endothelial cell growth factor). The cytokines and locally released enzymes cause the breakdown of the vessel walls of arterioles and venules, and sprouting of cells, including pericytes in the vessel wall. Endothelial cells proliferate and migrate out of the vessel into the tissue. They reorganise to form capillaries which interconnect (anastemosis) and link to venules, thereby forming a new capillary network.