The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

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Research Grants 2005-2006

Identification of cell lines for use in in vitro assays for sensitization

Geert Verheyen, PhD
VITO - The Flemish Institute for Technological Research

Many chemicals can induce allergic contact dermatitis (ACD) in susceptible individuals. ACD represents an important occupational and consumer health problem and there is need for reliable methods that permit the prospective identification of chemical allergens. This is currently done by animal testing, but the availability of validated in vitro models is of high importance for the industry (cosmetics, pharmaceuticals, pesticides, ...). A promising in vitro alternative to animal testing is the use of human antigen presenting cells (APC). APC are essential in the initiation of allergic reactions. Unfortunately, APC that are currently used (e.g. CD34-derived dendritic cells (CD34-DC)) are obtained from peripheral blood or cord blood samples from donors, and have several drawbacks that limit their potential (e.g. interindividual variation, low cell numbers, limited shelf life, ...). Ideal would be to have an immortal APC-like cell line that can be used to develop high-throughput in vitro assays. Several candidate cell lines have been described in the literature, such as MUTZ-3, THP-1 and U-937 cells. Here we will use gene expression microarray analyses to compare these 3 cell lines after exposing them to model chemical allergens (e.g. DNCB, Nickel). The observed effects on gene expression will be compared to our already available data, derived from exposing CD34-DC to the same chemical allergens. The goal of this study is to identify the most relevant cell line (i.e. resembling CD34-DC) that can be used for the development of an in vitro assay for the identification of chemical allergens.