Repair of damaged tissues occurs by two types of reactions: regeneration by proliferation of residual (uninjured) cells and maturation of tissue stem cells, and the deposition of connective tissue to form a scar (
Fig. 3.23 • Regeneration. Some tissues are able to replace the damaged components and essentially return to a normal
Mild, superficial injury Severe injury
Fig. 3.23 Mechanisms of tissue repair: regeneration and scar formation. Following mild injury, which damages the epithelium but not the underlying tissue, resolution occurs by regeneration, but after more severe injury with damage to the connective tissue, repair is by scar formation.
state; this process is called regeneration. Regeneration occurs by proliferation of cells that survive the injury and retain the capacity to proliferate, for example, in the rapidly dividing epithelia of the skin and intestines, and in some parenchymal organs, notably the liver. In other cases, tissue stem cells may contribute to the restoration of damaged tissues. However, whereas lower animals such as salamanders and fish can regenerate entire limbs or appendages, mammals have a limited capacity to regenerate damaged tissues and organs, and only some components of most tissues are able to fully restore themselves.
• Connective tissue deposition (scar formation). If the injured tissues are incapable of complete restitution, or if the supporting structures of the tissue are severely damaged, repair occurs by the laying down of connective (fibrous) tissue, a process that may result in formation of a scar. Although the fibrous scar is not normal, it provides enough structural stability that the injured tissue is usually able to function. The term fibrosis is most often used to describe the extensive deposition of collagen that occurs in the lungs, liver, kidney, and other organs as a consequence of chronic inflammation, or in the myocardium after extensive ischemic necrosis (infarction). If fibrosis develops in a tissue space occupied by an inflammatory exudate, it is called organization (as in organizing pneumonia affecting the lung).
After many common types of injury, both regeneration and scar formation contribute in varying degrees to the ultimate repair. Both processes involve the proliferation of various cells, and close interactions between cells and the extracellular matrix (ECM). We first discuss the general mechanisms of cellular proliferation and regeneration, and then the salient features of regeneration and healing by scar formation, and conclude with a description of cutaneous wound healing and fibrosis (scarring) in parenchymal organs as illustrations of the repair process.
The regeneration of injured cells and tissues involves cell proliferation, which is driven by growth factors and is critically dependent on the integrity of the extracellular matrix, and by the development of mature cells from stem cells. Before describing examples of repair by regeneration, we discuss the control of cell proliferation in this process. The general principles of cell proliferation were summarized in Chapter 1.
Cell Proliferation: Signals and Control Mechanisms
Several cell types proliferate during tissue repair. These include the remnants of the injured tissue (which attempt to restore normal structure), vascular endothelial cells (to create new vessels that provide the nutrients needed for the repair process), and fibroblasts (the source of the fibrous tissue that forms the scar to fill defects that cannot be corrected by regeneration).