title: The influence of stromal cells on the pigmentation of tissue-engineered dermo-epidermal skin grafts.
abstract: It has been shown in vitro that melanocyte proliferation and function in palmoplantar skin is regulated by mesenchymal factors derived from fibroblasts. In this study, we investigated in vivo the influence of mesenchymal-epithelial interactions in human tissue-engineered skin substitutes reconstructed from palmar- and nonpalmoplantar-derived fibroblasts. Tissue-engineered dermo-epidermal analogs based on collagen type I hydrogels were populated with either human palmar or nonpalmoplantar fibroblasts and seeded with human nonpalmoplantar-derived melanocytes and keratinocytes. These skin substitutes were transplanted onto full-thickness skin wounds of immunoincompetent rats. Four weeks after transplantation the development of skin color was measured and grafts were excised and analyzed with regard to epidermal characteristics, in particular melanocyte number and function. Skin substitutes containing palmar-derived fibroblasts in comparison to nonpalmoplantar-derived fibroblasts showed (a) a significantly lighter pigmentation; (b) a reduced amount of epidermal melanin granules; and (c) a distinct melanosome expression. However, the number of melanocytes in the basal layer remained similar in both transplantation groups. These findings demonstrate that human palmar fibroblasts regulate the function of melanocytes in human pigmented dermo-epidermal skin substitutes after transplantation, whereas the number of melanocytes remains constant. This underscores the influence of site-specific stromal cells and their importance when constructing skin substitutes for clinical application.
authors.affiliation: 1 Tissue Biology Research Unit, University Children's Hospital Zurich , Zurich, Switzerland .
authors.forename: Thomas
authors.initials: T
authors.lastname: Biedermann
authors.forename: Sophie
authors.initials: S
authors.lastname: Böttcher-Haberzeth
authors.forename: Agnieszka S
authors.initials: AS
authors.lastname: Klar
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Widmer
authors.forename: Luca
authors.initials: L
authors.lastname: Pontiggia
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Weber
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Weber
authors.forename: Clemens
authors.initials: C
authors.lastname: Schiestl
authors.forename: Martin
authors.initials: M
authors.lastname: Meuli
authors.forename: Ernst
authors.initials: E
authors.lastname: Reichmann
mesh_terms: D000293:Adolescent; D000818:Animals; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D020405:Dermis / Q000166:cytology / Q000637:transplantation*; D004817:Epidermis / Q000637:transplantation*; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007223:Infant; D053534:Keratin-9 / Q000378:metabolism; D008297:Male; D020460:Melanosomes / Q000378:metabolism; D010858:Pigmentation; D011923:Rats, Nude; D016038:Skin Transplantation; D017768:Skin, Artificial; D017154:Stromal Cells / Q000166:cytology; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D053534:Keratin-9