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First published online January 30, 2004
doi: 10.1242/10.1242/jcs.01005

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Fibroblast heterogeneity: more than skin deep

Skeletal Research Center, Biology Department, Case Western Reserve University, Cleveland, OH 44106, USA

View larger version (34K): [in a new window]   Fig. 1. Adult human skin is a layered organ consisting of an epidermis that is attached to a dermis by an elaborate connective tissue structure, the basement membrane (BM). The basal surface of the epidermis is indented by dermal and vascular components called dermal papillae (*). The dermis is divided into two functional layers, the papillary dermis and reticular dermis. These two layers are separated by a vascular plexus, the rete subpapillare. This plexus is fed by another vascular plexus, the rete cutaneum, located at the base of the reticular dermis. Skin also contains hair follicles (HF) and glands (not shown). Two distinct populations of dermal fibroblasts have been cultured from the interfollicular dermis, the region between hair follicles. Papillary fibroblasts (PF) are cultured from skin dermatomed at a depth of 0.3 mm and reticular fibroblasts (RF) are cultured from skin located at a depth below 0.7 mm. Hair follicle fibroblasts are obtained by carefully plucking or dissecting hairs from the skin and then placing these hairs or segments of these hair follicles onto surfaces of plastic culture dishes. Hair follicles contain two subsets of cells: the follicular sheath cells and dermal papilla cells.

View larger version (141K): [in a new window]   Fig. 2. The papillary and reticular dermis is separated by a vascular plexus, the rete subpapillare. The papillary dermis contains a higher density of cells than does the reticular dermis. Dermal papillae extend the surface area of the epithelial-mesenchymal boundary. Bar, 45 µm.

View larger version (129K): [in a new window]   Fig. 3. Immunohistochemical studies indicate that the papillary dermis (Pap) contains high levels of the proteoglycan decorin (A). The reticular dermis (Retic) contains elastic fibers oriented parallel to the epidermis that contain the proteoglycan versican. Microfibrils containing versican are also present in the papillary dermis as is diffuse versican at the DEJ (panel B). The epidermis (E) does not contain detectable levels of these two proteoglycans. The dashed line indicates the approximate demarcation between the papillary and reticular layers (adapted from Sorrell et al., 1999a, with kind permission from Kluwer Academic Publishers). Bar, 87 µm.

View larger version (154K): [in a new window]   Fig. 4. A skin equivalent consists minimally of a dermal equivalent and differentiated epidermis cultured first submerged then at the air-liquid interface in a three-dimensional context. Fibroblasts (arrows) encased in a type I collagen lattice provide dermal support for the epidermis. The epidermis is stratified and contains differentiated layers typically found in normal skin, including the (1) basal, (2) spinous, (3) granular and (4) cornified layers. Bar, 44 µm.

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