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Connective tissue provides a matrix supporting and physically connecting other tissues and cells to form the organs of the body. The interstitial fluid of connective tissue gives metabolic support to cells, serving as the direct medium for diffusion of nutrients and waste products.

Unlike the other tissue types (epithelium, muscle, and nerve) which consist mainly of cells, connective tissues always include very large amounts of extracellular matrix (ECM). Extracellular matrices contain different combinations of long protein fibers (collagen and elastic fibers) and ground substance, a complex of anionic hydrophilic proteoglycans, glycosaminoglycans (GAGs), and multiadhesive glycoproteins (laminin, fibronectin, and others). As described briefly in Chapter 4 with the basal lamina, such glycoproteins help stabilize the ECM by binding to other matrix components and to integrins in cell membranes. Water within ground substance allows the exchange of nutrients and metabolic wastes between cells and the blood supply.

The variety of connective tissue types in the body reflects differences in composition and amount of the cells, fibers, and ground substance, which together are responsible for the remarkable structural, functional, and pathologic diversity of connective tissue.

All connective tissues originate from embryonic mesenchyme, a tissue developing mainly from the middle layer of the embryo, the mesoderm. Mesenchyme consists largely of viscous ground substance with few collagen fibers (Figure 5–1). Mesenchymal cells have large nuclei with fine chromatin and prominent nucleoli. Often described as “spindle-shaped,” with their scant cytoplasm extended as two or more thin cytoplasmic processes, mesenchymal cells appear undifferentiated and evenly scattered through the ECM. Mesodermal cells migrate from their site of origin in the embryo, surrounding and penetrating developing organs. In addition to producing all types of connective tissue proper and the specialized connective tissues, bone and cartilage, the embryonic mesenchyme includes stem cells for other tissues, such as blood, the vascular endothelium, and muscle. This chapter describes the features of soft, supportive connective tissue proper.


Embryonic mesenchyme.

Mesenchyme consists of a population of undifferentiated cells, generally elongated but with many shapes, having large euchromatic nuclei and prominent nucleoli indicating high levels of synthetic activity. These mesenchymal cells are surrounded by an ECM they produced consisting largely of a simple ground substance rich in hyaluronan (hyaluronic acid), but with very little collagen. (×200; Mallory trichrome)


Some cells in mesenchyme are multipotent stem cells potentially useful in regenerative medicine after grafting to replace damaged tissue in certain patients. Mesenchyme-like cells remain present in some adult connective tissues, including that of tooth pulp and some adipose tissue, and are being investigated as possible sources of stem cells for therapeutic repair and organ regeneration.


Fibroblasts are the key cells in connective tissue proper (Figure 5–2 and Table 5–1...

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