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RECONSTRUCTION IN VITRO OF HUMAN SKIN FOR PHARMACOLOGICAL AND TOXICOLOGICAL STUDIES

Objective

A BETTER UNDERSTANDING OF THE RELATIONSHIP BETWEEN CELLS AND THE MATRIX IN A RECONSTRUCTED TISSUE COULD OPEN A NEW FIELD FOR EVALUATING TOXICOLOGICAL AND PHARMACOLOGICAL PROPERTIES IN VITRO.
The development of a living human skin equivalent, made of a dermis reconstructed by embedding fibroblasts in a 3-dimensional collagen network overlaid by keratinocytes, allowed the study of the physiology of differentiated cells and their response to pharmaco-toxicological agents in defined cell cell and cell matrix interactions.

The model enabled the study of the regulation of cell density in a tissue, the influence of the substrate on attachment, proliferation and protein synthesis, and collagen and collagenase gene expression in fibroblasts at a transcriptional or pretranslational level. The dermal equivalent is a model for skin ageing, wound contraction and studies on pathological fibroblasts. The covering of the dermal equivalent by an epidermis leads to models of epidermal wound healing, pigmentation and epidermal ageing. In addition, dermal epidermal interactions can be investigated. This human living skin equivalent, in which cells communicate and differentiate as in vivo is a major tool for pharmacotoxicology. It enables the identification of the influence of cell cell, cell matrix and dermal epidermal interactions in response to pharmacological agents. A human dermal equivalent model has been developed by culturing cells in close contact with their physiological matrix molecules and with cell types usually adjacent in vivo.
CELLS AND CONNECTIVE TISSUE COMPONENTS FROM THE SKIN CAN BE ISOLATED AND INVESTIGATED SEPARATELY IN DIFFERENT ORGAN AND CELL CULTURE. THE INDIVIDUAL CONSTITUENTS CAN ALSO BE USED TO RECONSTITUTE IN VITRO A SKIN EQUIVALENT. THE RECONSTITUTION OF AN ARTIFICIAL DERMIS REQUIRES TWO MAJOR COMPONENTS : FIBROBLASTS AND CONNECTIVE TISSUE MATRIX. IN THIS MODEL, THE DIFFERENTIATION OF FIBROBLASTS BECOME SIMILAR TO THE IN VIVO SITUATION AND QUITE DIFFERENT FROM FIBROBLASTS CULTIVATED AS MONOLAYERS, WHICH ARE USUALLY USED FOR PHARMACOLOGICAL OR TOXICOLOGICAL STUDIES.
IT IS PROPOSED TO INVESTIGATE THE BASIC CELLULAR AND CELL MATRIX INTERACTIONS EXPRESSED IN THIS MODEL, AS COMPARED WITH IN VIVO CONDITIONS AND OTHER IN VITRO CULTURE SYSTEMS, AND TO EVALUATE THE POTENTIALITY OF THIS MODEL FOR TOXICOLOGICAL AND PHARMACOLOGICAL STUDIES.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

UNIVERSITÉ DE LIEGE
Address
Place Du Xx Août 7
Liege
Belgium

Participants (4)

Hôpital Henri Mondor
France
Address

94010 Créteil
LUDWIG-MAXIMILIANS UNIVERSITY OF MUNICH
Germany
Address
Geschwister-scholl-platz 1
80539 Muenchen
St Thomas's Hospital Medical School
United Kingdom
Address
Lambeth Palace Road
London
University of Wales College of Medicine
United Kingdom
Address
Heath Park
CF4 4XN Cardiff