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The influence of stromal cells on the pigmentation of tissue-engineered dermo-epidermal skin grafts


Biedermann, Thomas; Böttcher-Haberzeth, Sophie; Klar, Agnieszka S; Widmer, Daniel S; Pontiggia, Luca; Weber, Andreas D; Weber, Daniel M; Schiestl, Clemens; Meuli, Martin; Reichmann, Ernst (2015). The influence of stromal cells on the pigmentation of tissue-engineered dermo-epidermal skin grafts. Tissue Engineering. Part A, 21(5-6):960-969.

Abstract

It has been shown in vitro that melanocyte proliferation and function in palmoplantar skin is regulated by mesenchymal factors derived from fibroblasts. Here, we investigated in vivo the influence of mesenchymal-epithelial interactions in human tissue-engineered skin substitutes reconstructed from palmar- and non-palmoplantar-derived fibroblasts. Tissue-engineered dermo-epidermal analogs based on collagen type I hydrogels were populated with either human palmar or non-palmoplantar fibroblasts and seeded with human non-palmoplantar-derived melanocytes and keratinocytes. These skin substitutes were transplanted onto full-thickness skin wounds of immuno-incompetent 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 non-palmoplantar 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.

Abstract

It has been shown in vitro that melanocyte proliferation and function in palmoplantar skin is regulated by mesenchymal factors derived from fibroblasts. Here, we investigated in vivo the influence of mesenchymal-epithelial interactions in human tissue-engineered skin substitutes reconstructed from palmar- and non-palmoplantar-derived fibroblasts. Tissue-engineered dermo-epidermal analogs based on collagen type I hydrogels were populated with either human palmar or non-palmoplantar fibroblasts and seeded with human non-palmoplantar-derived melanocytes and keratinocytes. These skin substitutes were transplanted onto full-thickness skin wounds of immuno-incompetent 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 non-palmoplantar 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Clinic for Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2015
Deposited On:05 Jan 2015 17:06
Last Modified:08 Dec 2017 09:25
Publisher:Mary Ann Liebert
ISSN:1937-3341
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1089/ten.TEA.2014.0327
PubMed ID:25300246

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