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Electrical Impedance Spectroscopy Quantifies Skin Barrier Function in Organotypic In Vitro Epidermis Models.
van den Brink, N J M; Pardow, F; Meesters, L D; van Vlijmen-Willems, I; Rodijk-Olthuis, D; Niehues, H; Jansen, P A M; Roelofs, S H; Brewer, M G; van den Bogaard, E H; Smits, J P H.
Afiliación
  • van den Brink NJM; Department of Dermatology, Radboudumc, Nijmegen, The Netherlands.
  • Pardow F; Department of Dermatology, Radboudumc, Nijmegen, The Netherlands.
  • Meesters LD; Department of Molecular Developmental Biology, Faculty of Science, Radboud University, Nijmegen, The Netherlands.
  • van Vlijmen-Willems I; Department of Dermatology, Radboudumc, Nijmegen, The Netherlands.
  • Rodijk-Olthuis D; Department of Molecular Developmental Biology, Faculty of Science, Radboud University, Nijmegen, The Netherlands.
  • Niehues H; Department of Dermatology, Radboudumc, Nijmegen, The Netherlands.
  • Jansen PAM; Department of Dermatology, Radboudumc, Nijmegen, The Netherlands.
  • Roelofs SH; Department of Dermatology, Radboudumc, Nijmegen, The Netherlands.
  • Brewer MG; Department of Dermatology, Radboudumc, Nijmegen, The Netherlands.
  • van den Bogaard EH; Locsense B.V., Enschede, The Netherlands.
  • Smits JPH; Department of Dermatology, University of Rochester Medical Center, Rochester, New York, USA.
bioRxiv ; 2024 Mar 19.
Article en En | MEDLINE | ID: mdl-38562885
ABSTRACT
3 D human epidermal equivalents (HEEs) are a state-of-the-art organotypic culture model in pre-clinical investigative dermatology and regulatory toxicology. Here, we investigated the utility of electrical impedance spectroscopy (EIS) for non-invasive measurement of HEE epidermal barrier function. Our setup comprised a custom-made lid fit with 12 electrode pairs aligned on the standard 24-transwell cell culture system. Serial EIS measurements for seven consecutive days did not impact epidermal morphology and readouts showed comparable trends to HEEs measured only once. We determined two frequency ranges in the resulting impedance spectra a lower frequency range termed EISdiff correlated with keratinocyte terminal differentiation independent of epidermal thickness and a higher frequency range termed EISSC correlated with stratum corneum thickness. HEEs generated from CRISPR/Cas9 engineered keratinocytes that lack key differentiation genes FLG, TFAP2A, AHR or CLDN1 confirmed that keratinocyte terminal differentiation is the major parameter defining EISdiff. Exposure to pro-inflammatory psoriasis- or atopic dermatitis-associated cytokine cocktails lowered the expression of keratinocyte differentiation markers and reduced EISdiff. This cytokine-associated decrease in EISdiff was normalized after stimulation with therapeutic molecules. In conclusion, EIS provides a non-invasive system to consecutively and quantitatively assess HEE barrier function and to sensitively and objectively measure barrier development, defects and repair.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos