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Animal experimentation

In vitro epidermis

   

In a first of its kind, a team of researchers from L'Oréal working on a European project has constructed synthetic skin which is sensitive to ultraviolet rays and has functional immune cells. It is already providing a new tool for the in vitro study of allergies and may one day help eliminate the need for experiments on animals.

     
   

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Histological section of a synthetic epidermis containing Langerhans cells and melanocytes.

"In vitro dermatology began in 1975," explains Rainer Schmidt, a researcher at L'Oréal. "That was when a US laboratory first described a technique for reproducing keratinocytes in culture." The principal cells of the epidermis, keratinocytes multiply, transform(1) and migrate to the surface, forming the skin's tough outer layer. This provides the barrier which protects us against injury and dehydration.

Until the early 1990s, synthetic skins consisted of keratinocytes but not melanocytes or Langerhans cells. The former synthesise the melanin which is responsible for tanning the skin and protecting it against the sun's rays; the latter play a vital role in immunological functions.

From the tanned prototype ...
In 1992, the L'Oréal laboratories, in cooperation with a number of research teams, succeeded in adding melanocytes to their prototype skin. As a result, the cultured epidermis was able to "tan" when exposed to UV radiation. This allowed the researchers to study the effects of various substances on the quality of the epidermis in detail and to measure exactly how much protection a sun-screen lotion provides. Specific products designed for precise skin types were subsequently developed using melanocytes taken from skins of different ethnic origin.

These early examples did not, however, allow the researchers to study the various immunological functions of the epidermis - the origin of over-sensitivity and allergies. In order to complete the synthetic skin, Langerhans cells had to be introduced. These are derived from "progenitor" cells produced in bone marrow. When released into the blood, they differentiate to a wide variety of cell types and migrate to the epidermis. It is the extent of this differentiation which makes it impossible to add them to synthetic skin from a biopsy.

... to immune responses
In 1997, while working on an EU-backed research project,(2) the coordinator, Rainer Schmidt, became the first person to succeed in producing synthetic skin containing keratinocytes, melanocytes and Langerhans cells.(3) The team used progenitor cells taken from umbilical cord blood, where these cells are particularly numerous. "We were afraid that the progenitor cells would not differentiate, because we knew nothing about this process. We initially planned for several intermediary stages before realising that, in reality, it is the keratinocytes themselves which control the differentiation and the implantation of the Langerhans cells."

When they exposed the synthetic skin to UV radiation, researchers were able to observe the disappearance of the Langerhans cells, which migrated out of the epidermis, demonstrating this phenomenon linked to UV-exposure-related immunosuppression for the first time in vitro. The project also showed that Langerhans cells change form and migrate when exposed to a powerful allergen, while remaining insensitive to a simple irritant. There is every indication that this "model" skin really works. "We have taken a step which will allow us to use this model in order to better study and understand the role played by the epidermis' cells in a contact allergy," concludes Rainer Schmidt. "And we now have human cells available which we can subject to any kind of treatment we like. I can tell you that I much prefer working with synthetic skin than with an animal, no matter what species."

(1) The so-called cellular differentiation phenomenon.
(2) New immuno-pharmaco-toxicological model: human reconstructed epidermis containing Langerhans cells. This project was supported by the Biotech programme (Fourth Framework Programme).
(3) This technique has since been patented.


Contact

Rainer Schmidt
Fax: +33-1-47567965
rschmidt@recherche.loreal.com

 

     
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