The Journal of investigative dermatology
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J. Invest. Dermatol. · Dec 1998
Living skin substitutes: survival and function of fibroblasts seeded in a dermal substitute in experimental wounds.
The healing of full-thickness skin defects requires extensive synthesis and remodeling of dermal and epidermal components. Fibroblasts play an important role in this process and are being incorporated in the latest generation of artificial dermal substitutes. We studied the fate of fibroblasts seeded in our artificial elastin/collagen dermal substitute and the influence of the seeded fibroblasts on cell migration and dermal substitute degradation after transplantation to experimental full-thickness wounds in pigs. ⋯ In conclusion, cultured dermal fibroblasts seeded in an artificial dermal substitute and transplanted onto full-thickness wounds in pigs survived and proliferated. The observed effects of seeded fibroblasts on dermal regeneration appeared to be mediated by reducing subcutaneous fibroblastic cell migration and/or proliferation into the wounds without impairing migration of monocytes/macrophages and endothelial cells. Moreover, the degradation of the implanted dermal substitute was retarded, indicating a protective activity of the seeded fibroblasts.
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J. Invest. Dermatol. · Dec 1998
Comparative StudyMIG is a dominant lymphocyte-attractant chemokine in lichen planus lesions.
Dense accumulation of mononuclear cells (lymphocytes > macrophages) in the dermal-epidermal interface and a T cell-mediated cytotoxic reaction against basal keratinocytes are hallmarks of lichen planus lesions. In this study, we focused on the chemotactic signals responsible for the selective recruitment of these cells. Using in situ hybridization and immunohistochemistry, the expression and localization of the lymphocyte-and/or monocyte/macrophage-attractant CC chemokines macrophage chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed, and secreted (RANTES), macrophage inflammatory protein-1alpha and -1alpha (MIP-1alpha/beta), I-309 and the CXC chemokines monokine induced by interferon-gamma (MIG), interferon-gamma-inducible protein-10 (IP-10), interleukin-8 (IL-8), epithelial-derived neutrophil attractant-78, and growth-related oncogene-alpha were investigated. ⋯ With more than 11% of total cells strongly expressing MIG transcripts, this selectively lymphotactic chemokine was by far the dominant chemokine and thus may significantly contribute to the inflammatory reaction in lichen planus lesions. According to the mRNA expression profiles, MIG, IP-10, and MCP-1 were expressed by both basal keratinocytes above and mononuclear cells within the inflammatory foci. Our findings indicate that a set of chemokines composed of IP-10, MCP-1, RANTES, MIP-1alpha, and especially MIG contributes to the cytokine network and preferential trafficking of mononuclear cells to the interface region of lichen planus lesions.
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J. Invest. Dermatol. · Nov 1998
Androgen-dependent beard dermal papilla cells secrete autocrine growth factor(s) in response to testosterone unlike scalp cells.
Androgens stimulate many hair follicles, e.g., beard, but may cause regression on the scalp; occipital areas are considered androgen independent. The mesenchyme-derived dermal papilla that regulates the hair follicle is considered the site of androgen action. Because hair size has been clearly related to dermal papilla size, one of the key functions androgens must regulate is the size of the dermal papilla. ⋯ Thus, both beard and scalp cells release similar autocrine growth factor(s), but their response to these factor(s) is determined by their in vivo origin. Testosterone in vitro stimulates secretion of an autocrine growth factor(s) by beard, but not scalp cells, to which only beard cells are able to respond, reflecting the responses to androgens in vivo. These factors may be involved in the key increase of dermal papilla size necessary for androgen-induced changes in hair size.
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J. Invest. Dermatol. · Aug 1998
Characterization of epidermal wound healing in a human skin organ culture model: acceleration by transplanted keratinocytes.
Few data are available on early regeneration of human epidermis in vivo. We have established a supravital skin organ culture model for epidermal wound healing by setting a central defect (3 mm diameter) in freshly excised skin specimens and culturing under air exposure. Re-epithelialization was followed for up to 7 d by histology and immunohistologic analysis of various markers for differentiation and proliferation. ⋯ At this stage, not only hyperproliferative (CK 6) but also, abundantly, maturation-associated cytokeratins (CK 1, CK 10) were detected immunohistochemically. Analyses of regenerated epidermis after transplantation of (i) keratinocytes labeled in vitro with BrdU and (ii) heterosexual keratinocytes by immunohistochemistry and fluorescence in situ hybridization for the Y chromosome, respectively, clearly showed that external keratinocytes are physically integrated into the regenerated epidermis and extendedly contribute to its formation. The data presented here demonstrate improvement and acceleration of epidermal re-epithelialization by transplantation of keratinocytes.