ABSTRACT
Some similarities in the spatial organization of cells of different tissues are apparent. Epithelial cells are a protective and regulatory barrier not just for skin but for all surfaces exposed to blood or to the external environment (e.g., respiratory tract, tubular digestive tract). These cells rest atop a selectively permeable
basement membrane. The composition of the underlying tissue varies, but it contains a connective tissue framework for parenchymal cells. If the tissue is an artery or a vein, the underlying connective tissue is composed of circularly arranged smooth-muscle cells which in turn are surrounded by an adventitia of loose connective tissue. Tissues within organs are generally organized into functional units around capillaries which facilitate metabolite and blood gas transport by virtue of their lack of a smooth muscle
layer (
tunica media
) and the thinness of their adventitial covering. Connective tissue cells of the tissue underlying capillaries deposit extracellular matrix (ECM) which is a mixture of fibrous proteins (collagens) embedded in a hydrated gel of glycosaminoglycans (GAGs). The GAGs, as distinguished by their sugar residues, are divided into five groups: hyaluronic acid, the chondiotin sulfates, dermatan sulfate, heparan and heparin sulfate, and keratan sulfate. All the GAGs except hyaluronic acid link with proteins to form proteoglycans. These proteoglycans bind to long-chained hyaluronic acid cores that interweave the cross-linked collagen fibers that form the framework of the tissue. The basic composition and density of deposition of stromal cell-derived ECM varies from tissue to tissue [Lin and Bissel, 1993]. Figure 18.2 is a scanning electron micrograph (SEM) depicting the intricacies of the ECM deposited by human bone marrow-derived stromal cells growing on a three-dimensional culture template. The ECM forms a sievelike arrangement for diffusion in an aqueous environment and a number of bone marrow-derived migratory cells are present as well. Such an arrangement dramatically enhances the surface area for cell growth. Although these voids are primarily filled by parenchymal cells, normal tissue interstitium also contains migratory immunocompetent cells such as B lymphocyte/plasma cells, T cells, and natural killer cells as well as the ubiquitous macrophage (histiocyte). The numbers of these cells are enhanced during inflammatory episodes when neutrophils or other granulocytes and/or mononuclear leukocytes infiltrate the tissue. Cytokines and other proteins released by these leukocytes recruit stromal cells in the tissue repair process. This phenomenon can be exploited by tumor cells to enhance their invasiveness (see Section 18.2 Tumor Cells). Although tissue function
in toto
is measured by parenchymal cell output (e.g., for liver, protein synthesis, metabolism; for bone marrow, blood cell production), this is profoundly influenced by and in some instances orchestrated by the stromal cell microenvironment.
