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New immuno-pharmaco-toxicological model: human reconstructed epidermis containing langerhans cells

Objective



The effort aiming at the use of improved reconstructed skin models as an alternative to animal testing has considerably increased in order to meet the January 1, 1998 deadline (Directive 93/35 EC) at which it will be prohibited in the European Union to sale cosmetic products containing ingredients or combinations of ingredients which have been tested on animals. A major problem, to meet the above requirements, remains the evaluation of new compounds for their potential to cause allergic contact dermatitis (sensitization), which still requires the use of in-vivo tests, since the only industrially produced European model of reconstructed human epidermis is composed of keratinocytes only. A reconstructed human epidermis composed of keratinocytes, melanocytes and Langerhans cells (LC) would considerably enlarge its field of application and provide for the first time a model to be used not only for immuno-pharmaco- toxicological studies in the cosmetic, pharmaceutical, and chemical industry, but also in basic research to study the complex mechanisms of cell-cell interaction in the epidermis.
The objective of the present shared-cost RTD project is to develop an in-vitro biotechnical model for immuno-pharmaco- toxicological studies by introducing Langerhans cells into human reconstructed epidermis. For the first time, a reconstructed human epidermis will comprise, as in-vivo, keratinocytes, melanocytes and Langerhans cells.
Scientists from four internationally recognized research teams with complementary competence in the fields of LC research and in-vitro skin models will cooperate to realise the four major tasks of this project which include: (i) the definition of culture and maintenance conditions avoiding the spontaneous migration of LC, (ii) the identification of LC that will integrate and remain in the epidermal reconstruct, (iii) comparative in-vivo and in-vitro studies to study the efficacy of the LC integration, and (iv) a pre-validation to determine the potential of the new model as an immunopharmaco-toxicological tool. Protocols will be elaborated for the large scale production and use of the model (kit). The elaborated protocols and experimental procedures will be communicated to ECVAM ( European Center for Validation of Alternative Methods) in view of pre- validation and eventually international validation of this biotechnical model.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

L'Oréal SA
Address
90,Rue Du Général Roguet
92110 Clichy
France

Participants (2)

Institut National de la Santé et de la Recherche Médicale
France
Address
Place D'arsonval
69437 Lyon
Karolinska Institute
Sweden
Address

171 76 Huddinge