Human skin explant model for the investigation of topical therapeutics

Jessica E Neil,Adrian C Williams,Marc B Brown

doi:10.1038/s41598-020-78292-4

Jessica E Neil, Adrian C Williams + Show 1 more

Open Access

https://doi.org/10.1038/s41598-020-78292-4

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Abstract

The development of in vitro and ex vivo models to mimic human illness is important not only for scientific understanding and investigating therapeutic approaches but also to mitigate animal testing and bridge the inter-species translational gap. While in vitro models can facilitate high-throughput and cost-efficient evaluation of novel therapeutics, more complex ex vivo systems can better predict both desirable and adverse in vivo effects. Here we describe an ex vivo cultured human skin explant model in which we have characterized pathological tissue integrity, barrier function and metabolic stability over time. Our findings suggest that human skin can be successfully cultured for pharmacodynamic use up to and beyond 9 days without any adverse physiological consequence.

Highlights

The development of in vitro and ex vivo models to mimic human illness is important for scientific understanding and investigating therapeutic approaches and to mitigate animal testing and bridge the inter-species translational gap
While some reports describe the cellular and morphological similarities and changes observed with human ex vivo skin culture, here we characterize the principle metabolic gene expression changes and correlate with the gross morphological changes to the tissue
The housekeeping genes r18s and cyclin-dependent kinase inhibitor 2A (CDKN2A) suggest a switch in metabolic activity on day 9

Summary

Introduction

The development of in vitro and ex vivo models to mimic human illness is important for scientific understanding and investigating therapeutic approaches and to mitigate animal testing and bridge the inter-species translational gap. From the 1980′s, reconstituted human epithelium (RHE) skin models were developed, in part for human irritancy studies These cultures allowed differentiation of an intact stratum corneum in an air–liquid interface that more closely resembled the in vivo human skin barrier. These models quickly gained interest for pharmacotoxicology studies and dermal irritation evaluation with commercially produced systems such as EpiSkin (L’Oreal) and EpiDerm (MatTek Corporation) available. These models still lack immune-associated cell types, either resident or carried by vascularisation, that are present with in vivo human skin clinical studies. Organ culture of human skin dates back over 50 years[6] and has undergone significant improvements to optimize the tissue for research studies developing therapeutics and formulations without the need for animal testing

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