TY  - JOUR
A1  - Hausmann, Christian
A1  - Zoschke, Christian
A1  - Wolff, Christopher
A1  - Darvin, Maxim E.
A1  - Sochorova, Michaela
A1  - Kovacik, Andrej
A1  - Wanjiku, Barbara
A1  - Schumacher, Fabian
A1  - Tigges, Julia
A1  - Kleuser, Burkhard
A1  - Lademann, Juergen
A1  - Fritsche, Ellen
A1  - Vavrova, Katerina
A1  - Ma, Nan
A1  - Schaefer-Korting, Monika
T1  - Fibroblast origin shapes tissue homeostasis, epidermal differentiation, and drug uptake
JF  - Scientific reports
N2  - 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 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.
Y1  - 2019
U6  - https://doi.org/10.1038/s41598-019-39770-6
SN  - 2045-2322
VL  - 9
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Wanjiku, Barbara
A1  - Yamamoto, Kenji
A1  - Klossek, Andre
A1  - Schumacher, Fabian
A1  - Pischon, Hannah
A1  - Mundhenk, Lars
A1  - Rancan, Fiorenza
A1  - Judd, Martyna M.
A1  - Ahmed, Muniruddin
A1  - Zoschke, Christian
A1  - Kleuser, Burkhard
A1  - Rühl, Eckart
A1  - Schäfer-Korting, Monika
T1  - Qualifying X-ray and Stimulated Raman Spectromicroscopy for Mapping Cutaneous Drug Penetration
JF  - Analytical chemistry
N2  - Research on topical drug delivery relies on reconstructed human skin (RHS) in addition to ex vivo human and animal skin, each with specific physiological features. Here, we compared the penetration of dexamethasone from an ethanolic hydroxyethyl cellulose gel into ex vivo human skin, murine skin, and RHS. For comprehensive insights into skin morphology and penetration enhancing mechanisms, scanning transmission X-ray microscopy (STXM), liquid chromatography tandem mass spectrometry (LC-MS/MS), and stimulated Raman spectromicroscopy (SRS) were combined. STXM offers high spatial resolution with label-free drug detection and is therefore sensitive to tissue damage. Despite differences in sample preparation and data analysis, the amounts of dexamethasone in RHS, detected and quantified by STXM and LC-MS/MS, were very similar and increased during the first 100 min of exposure. SRS revealed interactions between the gel and the stratum corneum or, more specifically, its protein and lipid structures. Similar to both types of ex vivo skin, higher protein-to-lipid ratios within the stratum corneum of RHS indicated reduced lipid amounts after 30 min of ethanol exposure. Extended ethanol exposure led to a continued reduction of lipids in the ex vivo matrixes, while protein integrity appeared to be compromised in RHS, which led to declining protein signals. In conclusion, LC-MS/MS proved the predictive capability of STXM for label-free drug detection. Combining STXM with SRS precisely dissected the penetration enhancing effects of ethanol. Further studies on topical drug delivery should consider the potential of these complementary techniques.
Y1  - 2019
U6  - https://doi.org/10.1021/acs.analchem.9b00519
SN  - 0003-2700
SN  - 1520-6882
VL  - 91
IS  - 11
SP  - 7208
EP  - 7214
PB  - American Chemical Society
CY  - Washington
ER  -