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

Scientific Reports
Christian HausmannMonika Schäfer-Korting

Abstract

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-year-olds 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...Continue Reading

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Citations

Feb 11, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Valerie S LeBleu, Eric G Neilson
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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
infrared spectroscopy
circumcision
PCR
Fluorescence

Software Mentioned

VisiSens
ImageJ
BZAnalyzer
VisiSens AnalytiCal 2

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