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. 2012 Jun 1;7(3):295-303.
doi: 10.1586/edm.12.24.

Human skin organ culture for assessment of chemically induced skin damage

James Varani  1
Affiliations

Human skin organ culture for assessment of chemically induced skin damage

James Varani. Expert Rev Dermatol. .

Abstract

The move away from animal models for skin safety testing is inevitable. It is a question of when, not if. As skin safety studies move away from traditional animal-based approaches, a number of replacement technologies are becoming available. Human skin in organ culture is one such technology. Organ-cultured skin has several features that distinguish it from other technologies. First and foremost, organ-cultured skin is real skin. Almost by definition, therefore, it approximates the intact skin better than other alternative models. Organ culture is an easy-to-use and relatively inexpensive approach to preclinical safety assessment. Although organ culture is not likely to replace high-throughput enzyme assays or monolayer culture/skin equivalent cultures for initial compound assessment, organ culture should find use when the list of compounds to be evaluated is small and when simpler models have narrowed the dose range. Organ-cultured skin also provides a platform for mechanistic studies.

Keywords: contact irritation; contact sensitization; corrosivity; organ culture; organotypic culture; skin.

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Conflict of interest statement

Financial & competing interests disclosure

The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1
Figure 1. Effects of retinoic acid on histology of human skin in organ culture
The control skin section on the left was incubated in a standard serum-free, growth factor-free culture medium for 8 days with fresh medium added at 2-day intervals. The section on the right was incubated under the same conditions but in addition treated with 1 µM RA during the 8-day incubation period (hematoxylin and eosin stained). See [23,24] for details. RA: Retinoic acid.
Figure 2
Figure 2. Effects of different contact sensitizers on histology of human skin in organ culture
The control skin section (upper left) was incubated in a standard serum-free, growth factor-free culture medium for 8 days with fresh medium added at 2-day intervals. The remaining sections were incubated under the same conditions but in addition treated with the indicated contact sensitizer (250 µM) during the 8-day incubation period (hematoxylin and eosin stained). See [35] for details. EGDM: Ethylene glycol dimethacrylate.
Figure 3
Figure 3. Amphiregulin levels in human skin organ culture fluid
Levels of the protein were assessed in day 2 culture fluids by enzyme-linked immunosorbant assay. The three contact irritants were used at concentrations of 1 µM (RA), 5 µM (SLS) and 10 µM (BZK), respectively. The five contact sensitizers were used at 250 µM. See [35] for details. BZK: Benzylkonium chloride; EGDM: Ethylene glycol dimethacrylate; RA: Retinoic acid; SLS: Sodium lauryl sulfate.
Figure 4
Figure 4. IL-6 levels in human skin organ culture fluid
Skin biopsies from eight subjects were maintained in organ culture for 2 days under control conditions and treated with RA or nickel sulfate. IL-6 levels were assessed by enzyme-linked immunosorbant assay. RA was used at 1 µM and nickel sulfate was tested at 500 µM. Values are from individual subjects. See [35] for details. RA: Retinoic acid.
See this image and copyright information in PMC

References

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Websites

    1. Mat Tech. Corp. www.mattek.com.
    1. Cell n Tec Advanced Cell Systems. www.cellntec.com.
    1. Organogenesis, Inc. www.organogenesis.com.
    1. Smith & Nephew. www.smith-nephew.com.