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Explant cultures of atopic dermatitis biopsies maintain their epidermal characteristics in vitro

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Abstract

Atopic dermatitis (AD) is a common inflammatory skin disorder characterised by various epidermal alterations. Filaggrin (FLG) mutations are a major predisposing factor for AD and much research has been focused on the FLG protein. Human skin equivalents (HSEs) might be useful tools for increasing our understanding of FLG in AD and to provide a tool for the screening of new therapies aimed at FLG replacement. Our aim is to establish an explant HSE (Ex-HSE) for AD by using non-lesional skin from AD patients wildtype for FLG or harbouring homozygous FLG mutations. These Ex-HSEs were evaluated as to whether they maintained their in vivo characteristics in vitro and whether FLG mutations affected the expression of various differentiation markers. FLG mutations did not affect the outgrowth from the biopsy for the establishment of Ex-HSEs. FLG expression was present in healthy skin and that of AD patients without FLG mutations and in their Ex-HSEs but was barely present in biopsies from patients with FLG mutations and their corresponding Ex-HSEs. AD Ex-HSEs and AD biopsies shared many similarities, i.e., proliferation and the expression of keratin 10 and loricrin, irrespective of FLG mutations. Neither KLK5 nor Lekti expression was affected by FLG mutations but was altered in the respective Ex-HSEs. Thus, Ex-HSEs established from biopsies taken from AD patients maintain their FLG genotype-phenotype in vitro and the expression of most proteins in vivo and in vitro remains similar. Our method is therefore promising as an alternative to genetic engineering approaches in the study of the role of FLG in AD.

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Authors and Affiliations

  1. Gorlaeus Laboratories, Department of Drug Delivery Technology, Leiden Academy Centre for Drug Research, Leiden University, Leiden, The Netherlands

    Vincent van Drongelen, Mogbekeloluwa O. Danso & Joke A. Bouwstra

  2. Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands

    Vincent van Drongelen, Jacoba J. Out, Aat Mulder, Adriana P. M. Lavrijsen & Abdoelwaheb El Ghalbzouri

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  1. Vincent van Drongelen
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  2. Mogbekeloluwa O. Danso
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  3. Jacoba J. Out
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  4. Aat Mulder
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  5. Adriana P. M. Lavrijsen
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  6. Joke A. Bouwstra
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  7. Abdoelwaheb El Ghalbzouri
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Correspondence to Vincent van Drongelen.

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Vincent van Drongelen and Mogbekeloluwa O. Danso share first authorship.

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van Drongelen, V., Danso, M.O., Out, J.J. et al. Explant cultures of atopic dermatitis biopsies maintain their epidermal characteristics in vitro. Cell Tissue Res 361, 789–797 (2015). https://doi.org/10.1007/s00441-015-2162-3

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  • DOI: https://doi.org/10.1007/s00441-015-2162-3

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