Development and Differentiation of Dermal Cells in Man

Abstract

Development and differentiation of the single free cells of mesenchyme and dermis of human embryos and fetuses from week 6 to term is described. From week 6 to week 14, three cell types are present: stellate general mesenchymal cells with long processes, phagocytic macrophages of probable yolk-sac origin, and a granule-secretory type of cell, which could be either a melanoblast or a mast stem cell. From week 14 to week 21, fibroblasts are numerous and active, and perineurial cells, pericytes, melanoblasts, mast cells, and Merkel cells can be individually identified. There is also present another cell type, possible of bone marrow origin, that may be ancestral to the Langerhans cell and that may be carried over into postanal dermis as the "histiocyte" or fixed dermal macrophage. From week 24 to term there is little change apart from the development of fat cells in the deeper dermis. Neither lymphocyte nor plasma cell was observed at any stage of development. These observations were used in the specification and identification of cells of fully developed postnatal dermis.

Dendritic Fibroblasts in Three-dimensional Collagen Matrices

“…Formation of a metabolically coupled, fibroblast dendritic network in collagen matrices is consistent with the in situ appearance of mesenchymal cells and skin fibroblasts (Breathnach, 1978;Trinkaus, 1984;Van Exan and Hardy, 1984;Omagari and Ogawa, 1990), which also are interconnected by gap junctions (Salomon et al, 1988;Warner, 1999). The fibroblast dendritic network has not been appreciated from earlier studies of cells in floating or restrained collagen matrices (Brown et al, 1998;Tranquillo, 1999;Grinnell, 2000;Tomasek et al, 2002), which were concerned primarily with the matrix contraction (i.e., global matrix remodeling).…”

“…The flattened, lamellar appearance characteristic of fibroblasts on planar surfaces differs markedly from the in situ appearance of mesenchymal cells and connective tissue fibroblasts, which tend to be stellate or dendritic in shape, often with long, slender extensions (Breathnach, 1978;Trinkaus, 1984;Van Exan and Hardy, 1984;Omagari and Ogawa, 1990;Beertsen et al, 2000). In part, the differences in appearance of fibroblasts on planar surfaces compared with tissue may be a reflection of topographic responsiveness (Trinkaus, 1984); cells can detect nanometric substratum surface features (Curtis and Wilkinson, 1999).…”

“…Small G proteins are particularly important in the process because of their diverse effects on the actin cytoskeleton (Hall, 1998;Kaibuchi et al, 1999). Activation of Rac (e.g., by platelet-derived growth factor [PDGF]) stimulates cell protrusion, whereas activation of Rho (e.g., by lysophosphatidic acid) inhibits cell protrusion and stimulates cell contraction (Clark et al, 1998;Rottner et al, 1999).The flattened, lamellar appearance characteristic of fibroblasts on planar surfaces differs markedly from the in situ appearance of mesenchymal cells and connective tissue fibroblasts, which tend to be stellate or dendritic in shape, often with long, slender extensions (Breathnach, 1978;Trinkaus, 1984;Van Exan and Hardy, 1984;Omagari and Ogawa, 1990;Beertsen et al, 2000). In part, the differences in appearance of fibroblasts on planar surfaces compared with tissue may be a reflection of topographic responsiveness (Trinkaus, 1984); cells can detect nanometric substratum surface features (Curtis and Wilkinson, 1999).…”

Cell–Matrix Entanglement and Mechanical Anchorage of Fibroblasts in Three-dimensional Collagen Matrices

“…Attached cells, rather than forming flattened, lamellar extensions as occurs on impenetrable glass or plastic surfaces, range in shape from dendritic to stellate to bipolar, depending on matrix stiffness and tension (Grinnell, 2003). Similar morphological features have been described for cells in tissues (Breathnach, 1978;Doljanski, 2004;Goldsmith et al, 2004;Langevin et al, 2005). In part, differences in morphology between cells in twodimensional (2D) versus 3D culture may result from the symmetric adhesive interactions in 3D matrices versus the forced asymmetry of 2D surfaces (Beningo et al, 2004).…”

Fibroblast mechanics in 3D collagen matrices☆

“…Cells in a pro-contractile, low tension state environment eventually re-protrude their extensions but in a more bipolar morphology [45]. Fibroblasts exhibiting dendritic/bipolar morphologies resemble tissue fibroblasts under resting conditions [46][47][48][49][50], whereas cells with prominent stress fibers and focal adhesions cannot typically be observed in tissues except during activated conditions such as wound repair and fibrosis [5][6][7][8].…”