18 November 2020

Skin regeneration at the flick of a switch

Scientists at BRAIN have demonstrated by a specially developed cell-based assay in the laboratory that bioactive substances from the BRAIN Bioarchive can activate skin cells. Industrial customers, e.g. from the cosmetics industry, can now use the test system to screen natural substances from the BRAIN substance library according to their specifications and thus find natural active ingredients for skin regeneration.

The constant volume of a cell is normally fundamental to the functions that the cell performs. Nevertheless, cells can change their volume, and that may be very useful. This is the case when, for example, cell development or proliferation is regulated. With natural substances from the BRAIN substance library, such regulation has been successfully achieved in vitro in an epidermal cell model. Dr. Torsten Fauth, scientist and project manager at BRAIN AG, reported on this at the IFSCC Conference 2020.

The ISFCC is the leading conference for cosmetic research with the highest scientific standards. Torsten Fauth therefore felt honored to have been invited one more time to report on his current research results. Two years earlier, the biologist had indeed received the IFSCC Award for Applied Research for his work. Torsten Fauth now presented his latest findings on the activation of ion channels in keratinocyte stem cells – a process that can be used to stimulate epidermal skin renewal. The focus was on an ion channel named "LRRC8A".

Our skin: Two square meters of protection

Our skin is exposed to various stress factors, e.g. high or low temperature, UV radiation, mechanical stress, but also pathogens. Such stress factors impair the skin's barrier function and can contribute to the development or worsening of skin diseases. Examples are atopic dermatitis or psoriasis. Maintaining skin function and supporting skin renewal thus contributes to health.

In order to understand how the natural skin renewal process takes place, it is advisable to first consider the structure of the different cell layers that contribute to skin renewal (see figure). These form the basis of a healthy epidermis when there is a balance between proliferation (cell division) and differentiation (cell specialization).

Structure of the epidermis from associated tissue layers. The arrows show the "migration" of cells in the course of their differentiation from keratinocyte stem cells to post-mitotic cells: from the inner basal layer to the outer epidermis.

Keratinocyte stem cells (KSC) are located in the basal layer of the epidermis (Stratum basale). Stem cells have the potential to further differentiate into specialized cells. The keratinocyte stem cells in the basal layer undergo several cell divisions for this purpose: A keratinocyte stem cell first becomes a kind of transition cell or “transient amplifying" (TA) cell. While the keratinocyte stem cells remain in place, the TA cells are able to "migrate": From the lower layer they migrate towards the upper epidermal layer and in the process transform again into so-called post-mitotic (PM) cells. These continue to develop and finally form the Stratum corneum layer, also called the “horny layer”, as the outermost layer.

What does the switch achieve?

The switch, i.e. the change from the keratinocyte stem cell to the TA cell, is a decisive event in the skin renewal process, and scientists at BRAIN wanted to find out – in cooperation with the Dermatology Department of the University Hospital Frankfurt – which "protagonists" are involved in this switch. They also hoped to find a point where this switch could be influenced to a greater or lesser extent. Because it is not only too little skin renewal that can cause skin problems; excessive skin renewal, as in psoriasis, may also engender pathology.

In fact, the team succeeded in identifying a family of ion channels that not only plays a major role in the regulation of the cell volume of keratinocytes, but also plays a role in differentiation. Parts of this research work have been published in the Experimental Dermatology journal (Trothe et al., 2018).

High-throughput testing of substances

Based on various preliminary studies, Fauth’s team developed a cell-based assay and tested natural and nature-identical substances from the BRAIN substance library in vitro in a pilot approach. Some of the substances were found to have specific bioactivity (so-called "skin cell activators") and are now further evaluated. The team was able to demonstrate using additional cell and molecular biological technologies that these bioactive substances not only stimulate the proliferation of keratinocyte stem cells, but also their differentiation.

Screening for the cosmetics industry

With their results, the scientists at BRAIN have provided a "proof of concept" for the fact that the investigated target molecule or "target" (LRRC8A) is important for the development and differentiation of skin cells − and that this development can be controlled or influenced by target modulators.

The Screenline® assay for mimicking the LRRC8 function in keratinocytes is an ideal in vitro model for identifying additional bioactive substances from BRAIN´s natural compounds library and to test their positive influence on skin regeneration. A patent application has been filed for the control of the ion channel to modulate the differentiation of skin cells (Ertongur-Fauth et al., 2019).

BRAIN would like to utilize the newly developed cell model to identify, in partnership with its customers, active substances that could be used as ingredients in cosmetic care products. Possible applications are stressed, aging, barrier-disturbed or inflamed skin (e.g. psoriasis or atopic dermatitis). The diverse BRAIN Substance Libraries as well as the customer's own resources can serve as a basis.

If you are interested or have any questions, please contact:

Business Development Skin Care

Grants and partners

Parts of the work of Fauth and his team were kindly supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the Natural Life Excellence 2020 Strategic Alliance (NatLifE2020).

We would like to thank our cooperation partners: the University Hospital Frankfurt (PD Dr. Claudia Bürger), the Technical University of Darmstadt (Dr. Oliver Rauh) and Nanion Technologies GmbH


Ertongur-Fauth, T., J. Trothe, and C. Buerger. 2019. The volume-regulated anion channel protein LRRC8A for use in altering keratinocyte differentiation. Patent Application WO 2019/158696

Trothe, J., D. Ritzmann, V. Lang, P. Scholz, U. Pul, R. Kaufmann, C. Buerger, and T. Ertongur-Fauth. 2018. Hypotonic stress response of human keratinocytes involves LRRC8A as component of volume-regulated anion channels. Experimental dermatology. https://doi.org/10.1111/exd.13789

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