Reporter Skin Models for the Investigation of Cell Stress Responses

We offer a portfolio of patented reporter skin models (EP 2 041 172) for the detection of typical cell stress responses such as inflammation, sensitization or ER stress – i.e. stress triggered by defective protein folding in the endoplasmic reticulum (ER).

These in-vivo reconstituted epidermal and full-thickness skin models with an intact skin barrier are based on immortalized primary keratinocytes, whose use guarantees high donor-independent reproducibility. The activation of a specific cellular stress signaling pathway in these immortalized primary keratinocytes can be read out quickly and easily via a reporter protein that has been stably integrated into the genome using a reporter construct. In this way, both skin-damaging and skin-regenerating or skin-protecting substance effects can be specifically identified and evaluated: 

Reporter skin models for the detection of anti-/inflammatory effects 

are reconstructed epidermis and full-thickness skin models based on NF-kB reporter keratinocytes for the evaluation of the inflammation-inducing or -inhibiting potential of substances via the activation of the NF-kB signaling pathway.

As a central mediator of inflammatory reactions, the transcription factor NF-kB induces the expression of various pro-inflammatory genes and is involved in the regulation of inflammasomes [1] .

Reporter skin models for the detection of sensitizing and anti-/oxidative effects

are reconstructed epidermal and full-thickness skin models based on Nrf2 reporter keratinocytes to assess the sensitizing/oxidative stress-inducing potential of substances via activation of the Nrf2 pathway.

The transcription factor NRf2 plays a crucial role as a master regulator in maintaining the cellular redox balance in the adaptive response to oxidative stress, which can lead to sensitization to the stress-inducing substance [2].

Reporter skin models for the detection of ER stress-inducing effects

are reconstructed epidermal and full-thickness skin models based on stress sensor keratinocytes to assess the ER stress-inducing potential of substances via activation of specific transcription factors that are significantly involved in cell stress. ER stress is caused by the accumulation of incorrectly folded proteins in the endoplasmic reticulum (ER) [3].

Challenge: proving the safety of cosmetics and chemicals

In order to guarantee the consumer safety of new chemical substances – as ingredients in cosmetics, cleaning agents, clothing, biocides, pesticides or as industrial chemicals – their safety for humans must be demonstrated before they are approved for the market. In-vitro tissue models, for example of the skin, are ideally suited to replace animal testing.

Our development: 3D skin model with barrier function

With our decades of experience in the development and targeted genetic modification of human cell lines, the establishment of human reconstituted 3D skin models and compliance with the highest quality standards, we establish specific reporter skin models that are suited for reliable testing of substances. Our reporter keratinocytes form a multilayered epidermis with full physiological skin barrier function in vitro and show a unique correspondence of characteristic differentiation markers of the models with native human skin.

Unique selling point: precise results on living tissue

Reporter skin models are ideally suited to obtaining precise results immediately and on living tissue when testing different substances. By genetically modifying the skin cells, we can differentiate between the most important cell stress responses such as inflammation, sensitization or oxidative stress and ER stress using different reporter skin models.

Whether a chemical substance damages human skin cells is visualized by means of a reporter protein secreted into the culture medium, which has been activated via the respective cellular signaling cascade, and can thus be read out quickly, easily and quantitatively. All that is required is the removal of a few microliters of the cultivation medium and the addition of a suitable substrate. 

Further advantages of our patented reporter skin models

• They are donor-independent and reproducible through the use of immortalized primary cells and available at any time,
• allow an investigation and comparison of substances in systemic and topical application,
• allow multiple sampling due to a reporter protein secreted into the culture medium and are thus suitable for investigating the time course of signaling pathway activation,
• enable more realistic exposure scenarios, as the substance to be tested can be applied directly onto the skin barrier, which also enables the testing of water-insoluble, viscous or (semi-)solid substances and the evaluation of mixtures of substances with different skin penetration properties,
• allow simultaneous investigation of the skin stress potential via the activation of various cellular stress signaling pathways, cytotoxicity and skin penetration of a substance in the same model,
• can be cultivated without media additives of animal origin, and
• allow investigations with repeated substance application.