A NOVEL SYSTEM FOR TESTING DERMAL AND EPIDERMAL TOXICITY IN VITRO

A THREE-DIMENSIONAL HUMAN SKIN MODEL HAS BEEN DEVELOPED IN OUR LABORATORY AND IS BEING CHARACTERIZED AND MODIFIED FOR USE IN CYTOTOXICITY ASSAYS, CHEMICAL PENETRATION STUDIES, AND ENGRAFTMENT STUDIES, AS A TARGET TISSUE IN DRUG MECHANISM STUDIES, AND AS A SOURCE FOR VARIOUS NATURALLY-SECRETED GROWTH FACTORS. THE MODEL CONSISTS OF A DERMAL LAYER OF FIBROBLASTS AND NATURALLY SECRETED COLLAGEN AND AN EPIDERMAL LAYER OF MELANOCYTES AND KERATINOCYTES. A DERMAL/EPIDERMAL JUNCTION IS PRESENT. THE SKIN MODEL INVOLVES USE OF A COMPLETELY MANIPULABLE MESHWORK AND REPRESENTS A MODEL SIMILAR TO THE IN VIVO SYSTEM IN TERMS OF CELL-CELL INTERACTIONS, NATURALLY SECRETEDMATRIX PROTEINS, PIGMENT PRODUCTION, SECRETION AND STORAGE, AND CELL MATURATION AND KERATINIZATION. THIS CULTURE METHOD IS INEXPENSIVE, DURABLE, NON-ANTIGENIC, NON-TOXIC, AND ALLOWS EXCELLENT CELL ADHERENCE. IT IS THE ONLY SKIN MODEL CURRENTLY AVAILABLE IN WHICH DERMAL FIBEROBLASTS REMAIN MITOTICALLY AND METABOLICALLY ACTIVE IN VITRO WHILE ACTIVELY SUPPORTING THE GROWTH AND DIFFERENTIATION OF EPIDERMAL CELLS. INITIAL FUNDING IS SOUGHT FOR THE FURTHER DEVELOPMENT AND CHARACTERIZATION OF THIS PHYSIOLOGICAL SKIN MODEL AS A SUBSTRATE FOR CYTOTOXICITY STUDIES AND AS A MODEL FOR SKIN PENETRATION ASSAYS FOR TOXINS AND PHARMACEUTICALS.