The human epidermis models EpiSkin®, SkinEthic® and EpiDerm®: An evaluation of morphology and their suitability for testing phototoxicity, irritancy, corrosivity, and substance transport

Netzlaff, Frank; Lehr, Claus‐Michael; Wertz, Philip W.; Schaefer, Ulrich F.

doi:10.1016/j.ejpb.2005.03.004

Cited by 321 publications

(232 citation statements)

References 43 publications

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“…The reconstructed tisThis paper was submitted directly (Track II) to the PNAS office. sues show lipid profiles similar to the corresponding tissue in vivo, release the relevant cytokines, and demonstrate the presence of gap junctions (21)(22)(23)(24).…”

Section: Methodsmentioning

confidence: 82%

“…1. These systems are generated by growing differentiated keratinocyte cultures on acellular or fibroblast-populated dermal substrates (20,21). One of the systems reconstructs the human epidermis, and the other is a ''full-thickness'' skin model corresponding to the epidermis and dermis of normal human skin.…”

Section: Methodsmentioning

confidence: 99%

“…Analysis of the tissue microstructure has demonstrated the presence of keratohyalin granules, tonofilament bundles, desmosomes, and a multilayered stratum corneum containing intercellular lamellar lipid layers arranged in patterns characteristic of the in vivo epidermis (22). The reconstructed tissues are mitotically and metabolically active, maintaining the same differentiation patterns as those in vivo (21,23). Markers of mature epidermis-specific differentiation such as profilaggrin, the K1͞K10 cytokeratin pair, involucrin, and type I epidermal transglutaminase, are expressed (24).…”

Section: Methodsmentioning

confidence: 99%

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Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away

Belyakov

Mitchell

Parikh

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

272

166

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A central tenet in understanding the biological effects of ionizing radiation has been that the initially affected cells were directly damaged by the radiation. By contrast, evidence has emerged concerning ''bystander'' responses involving damage to nearby cells that were not themselves directly traversed by the radiation. These long-range effects are of interest both mechanistically and for assessing risks from low-dose exposures, where only a small proportion of cells are directly hit. Bystander effects have been observed largely by using single-cell in vitro systems that do not have realistic multicellular morphology; no studies have as yet been reported in three-dimensional, normal human tissue. Given that the bystander phenomenon must involve cell-to-cell interactions, the relevance of such single-cell in vitro studies is questionable, and thus the significance of bystander responses for human health has remained unclear. Here, we describe bystander responses in a three-dimensional, normal human-tissue system. Endpoints were induction of micronucleated and apoptotic cells. A charged-particle microbeam was used, allowing irradiation of cells in defined locations in the tissue yet guaranteeing that no cells located more than a few micrometers away receive any radiation exposure. Unirradiated cells up to 1 mm distant from irradiated cells showed a significant enhancement in effect over background, with an average increase in effect of 1.7-fold for micronuclei and 2.8-fold for apoptosis. The surprisingly long range of bystander signals in human tissue suggests that bystander responses may be important in extrapolating radiation risk estimates from epidemiologically accessible doses down to very low doses where nonhit bystander cells will predominate.bystander ͉ normal human tissue ͉ radiological risk

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Section: Methodsmentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away

Belyakov

Mitchell

Parikh

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

272

166

View full text Add to dashboard Cite

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“…Forth, we did not observe any natural moisturizing factors (NMF) within the RHE models by Raman spectroscopy, while NMF molecules are detectable by Raman spectroscopy for human skin in vivo 2 . These differences may explain the different barrier properties of skin models and human skin, which have already been outlined in several investigations 14,40 .…”

Section: Untreated Samplesmentioning

confidence: 87%

Label free non-invasive imaging of topically applied actives in reconstructed human epidermis by confocal Raman spectroscopy

Fleischli

Mathes

Adlhart

2013

Vibrational Spectroscopy

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Raman spectroscopy has become a versatile tool for the in vivo charaterisation of skin. Here we describe use of Raman spectroscopy for high resolution optical cross sectioning to resolve skin constituents and administered drugs at the cellular level. Percutaneous penetration is typically studied using permeation cells with biopsies of animals or human skin. Although this technique provides valuable clinical data, little insight is gained in the microstructure of drug penetration (intercellular or transcellular) or in the mode of action of applied vehicles or penetration enhancers. Therefore, a Raman microspectroscopic method was combined with a confocal scanning setup to image the microstructure of commercially available skin models (SkinEthic®) and the spatial distribution of penetrated actives. The models' microstructure was scanned without any special treatment or environment such as cutting, staining, freezing, or application of vacuum. The non-invasive Raman images reveal the layered structure of stratum corneum. This in particular for lipids while water tends to be more evenly distributed. When penetration of the hydrophilic active glycerol and the lipophilic octyl methoxycinnamate, OMC, was studied, a strong correlation between the local distribution of skin constituents and the hydrophilic / lipophilic character of the active was observed.

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“…Given that false negatives are particularly infrequent when using this method, it can be considered suitable for the evaluation of phototoxicity. One application of 3T3 NRU PT testing is the evaluation of poorly water-soluble substances, for which an alternative method, a 3-dimensional cultured skin model, has also been proposed (Ceridono et al, 2012;Portes et al, 2002;Netzaff et al, 2005). Since 3T3 NRU PT can characteristically identify phototoxicological hazards with almost 100% specificity, it can be considered highly economical and easier to use than the 3-dimensional cultured skin model and was therefore used in this study to evaluate poorly water-soluble substances.…”

Section: Discussionmentioning

confidence: 99%

Development of a modified 3T3 Neutral Red Uptake Phototoxicity Test protocol for evaluation of poorly water-soluble substances

et al. 2017

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-The 3T3 neutral red uptake phototoxicity test (OECD TG432) is an alternative phototoxicity test method that is relatively easy and rapid to implement, with results obtainable in a short time, and is reported to have high reproducibility compared with in vivo assay methods. However, this method has been shown to be unsuitable for testing poorly water-soluble substances, which tend to separate out when mixed with the assay buffer solution. This causes difficulties in determining the dose dependency of substances and subsequent determination of the photoirritation factor because the ratio of cell viability, expressed as the half-maximal inhibitory concentration (IC 50 ) in the presence or absence of light, is not calculable. In this study, we investigated the optimum conditions for the evaluation of poorly water-soluble substances. In the conventional method, the final solvent concentration was 1% and the pre-incubation time was 60 min, but in the modified method, 10% and 5 min were used, respectively. Next, the results from the conventional method were compared with those of our modified method, which was found to be viable and comparable with the conventional method. Moreover, the false positive results frequently obtained with poorly water-soluble substances in the conventional method were not evident with the modified method, thus confirming its usefulness for the evaluation of such substances. We therefore propose that the modified method can be used for the in vitro testing of poorly water-soluble substances in phototoxicity evaluations.

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The human epidermis models EpiSkin®, SkinEthic® and EpiDerm®: An evaluation of morphology and their suitability for testing phototoxicity, irritancy, corrosivity, and substance transport

Cited by 321 publications

References 43 publications

Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away

Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away

Label free non-invasive imaging of topically applied actives in reconstructed human epidermis by confocal Raman spectroscopy

Development of a modified 3T3 Neutral Red Uptake Phototoxicity Test protocol for evaluation of poorly water-soluble substances

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