Fibroblasts (Figure1), the most common cells in connective tissue proper, produce and maintain most of the tissue’s extracellular components. Fibroblasts synthesize and secrete collagen (the most abundant protein of the body) and elastin, which both form large fibers, as well as the GAGs, proteoglycans, and multiadhesive glycoproteins that comprise the ground substance. As described later, most of the secreted ECM components undergo further modification outside the cell before assembling as a matrix.
Fig1. Fibroblasts
Distinct levels of fibroblast activity can be observed histologically (Figure 1b). Cells with intense synthetic activity are morphologically different from the quiescent fibroblasts that are scattered within the matrix they have already synthesized. Some histologists reserve the term “fibroblast” to denote the active cell and “fibrocyte” to denote the quiescent cell. The active fibroblast has more abundant and irregularly branched cytoplasm, containing much rough endoplasmic reticulum (RER) and a well developed Golgi apparatus, with a large, ovoid, euchromatic nucleus and a prominent nucleolus. The quiescent cell is smaller than the active fibroblast, is usually spindle-shaped with fewer processes, much less RER, and a darker, more heterochromatic nucleus.
Fibroblasts are targets of many families of proteins called growth factors that influence cell growth and differentiation. In adults, connective tissue fibroblasts rarely undergo division. However, stimulated by locally released growth factors, cell cycling and mitotic activity resume when the tissue requires additional fibroblasts, for example, to repair a damaged organ. Fibroblasts involved in wound healing, sometimes called myofibroblasts, have a well-developed contractile function and are enriched with a form of actin also found in smooth muscle cells.
MEDICAL APPLICATION
The regenerative capacity of connective tissue is clearly observed in organs damaged by ischemia, inflammation, or traumatic injury. Spaces left after such injuries, especially in tissues whose cells divide poorly or not at all (eg, cardiac muscle), are filled by connective tissue, forming dense irregular scar tissue. The healing of surgical incisions and other wounds depends on the reparative capacity of connective tissue, particularly on activity and growth of fibroblasts.
In some rapidly closing wounds, a cell called the myofibroblast, with features of both fibroblasts and smooth muscle cells, is also observed. These cells have most of the morphologic characteristics of fibroblasts but contain increased amounts of actin microfilaments and myosin and behave much like smooth muscle cells. Their activity is important for the phase of tissue repair called wound contraction.
