Fibroblast origin shapes tissue homeostasis, epidermal differentiation, and drug uptake

  • Preclinical studies frequently lack predictive value for human conditions. Human cell-based disease models that reflect patient heterogeneity may reduce the high failure rates of preclinical research. Herein, we investigated the impact of primary cell age and body region on skin homeostasis, epidermal differentiation, and drug uptake. Fibroblasts derived from the breast skin of female 20- to 30-yearolds or 60- to 70-year-olds and fibroblasts from juvenile foreskin (<10 years old) were compared in cell monolayers and in reconstructed human skin (RHS). RHS containing aged fibroblasts differed from its juvenile and adult counterparts, especially in terms of the dermal extracellular matrix composition and interleukin-6 levels. The site from which the fibroblasts were derived appeared to alter fibroblast-keratinocyte crosstalk by affecting, among other things, the levels of granulocyte-macrophage colony-stimulating factor. Consequently, the epidermal expression of filaggrin and e-cadherin was increased in RHS containing breast skinPreclinical studies frequently lack predictive value for human conditions. Human cell-based disease models that reflect patient heterogeneity may reduce the high failure rates of preclinical research. Herein, we investigated the impact of primary cell age and body region on skin homeostasis, epidermal differentiation, and drug uptake. Fibroblasts derived from the breast skin of female 20- to 30-yearolds or 60- to 70-year-olds and fibroblasts from juvenile foreskin (<10 years old) were compared in cell monolayers and in reconstructed human skin (RHS). RHS containing aged fibroblasts differed from its juvenile and adult counterparts, especially in terms of the dermal extracellular matrix composition and interleukin-6 levels. The site from which the fibroblasts were derived appeared to alter fibroblast-keratinocyte crosstalk by affecting, among other things, the levels of granulocyte-macrophage colony-stimulating factor. Consequently, the epidermal expression of filaggrin and e-cadherin was increased in RHS containing breast skin fibroblasts, as were lipid levels in the stratum corneum. In conclusion, the region of the body from which fibroblasts are derived appears to affect the epidermal differentiation of RHS, while the age of the fibroblast donors determines the expression of proteins involved in wound healing. Emulating patient heterogeneity in preclinical studies might improve the treatment of age-related skin conditions.show moreshow less

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Author details:Christian Hausmann, Christian Zoschke, Christopher Wolff, Maxim E. Darvin, Michaela Sochorova, Andrej Kovacik, Barbara Wanjiku, Fabian SchumacherORCiDGND, Julia Tigges, Burkhard KleuserORCiDGND, Juergen Lademann, Ellen Fritsche, Katerina VavrovaORCiD, Nan MaORCiD, Monika Schaefer-Korting
DOI:https://doi.org/10.1038/s41598-019-39770-6
ISSN:2045-2322
Pubmed ID:http://www.ncbi.nlm.nih.gov/pubmed?term=30814627
Title of parent work (English):Scientific reports
Publisher:Nature Publ. Group
Place of publishing:London
Publication type:Article
Language:English
Date of first publication:2019/02/27
Completion year:2019
Release date:2021/04/06
Volume:9
Page number:10
Funding institution:German Research FoundationGerman Research Foundation (DFG) [234930468]; Federal Ministry of Education and ResearchFederal Ministry of Education & Research (BMBF) [031A262A]; Elsa-Neumann doctoral scholarships; Czech Science FoundationGrant Agency of the Czech Republic [16-25687J]; Charles University [SVV260401]; German Research FoundationGerman Research Foundation (DFG); Open Access Publication Fund of the Freie Universitat Berlin
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie
DDC classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
License (German):License LogoCreative Commons - Namensnennung, 4.0 International