Tri-culture System for Pro-hapten Sensitizer Identification and Potency Classification

Overview

Journal Technology (Singap World Sci)

Date 2018 Dec 7

PMID 30519598

Citations 5

Authors

Serom Lee

Talia Greenstein

Lingting Shi

Tim Maguire

Rene Schloss

Martin Yarmush

Affiliations

Soon will be listed here.

Abstract

Allergic contact dermatitis (ACD) is an inflammatory disease that impacts 15-20% of the general population and accurate screening methods for chemical risk assessment are needed. However, most approaches poorly predict pre- and pro-hapten sensitizers, which require abiotic or metabolic conversion prior to inducing sensitization. We developed a tri-culture system comprised of MUTZ-3-derived Langerhans cells, HaCaT keratinocytes, and primary dermal fibroblasts to mimic the cellular and metabolic environments of skin sensitization. A panel of non-sensitizers and sensitizers was tested and the secretome was evaluated. A support vector machine (SVM) was used to identify the most predictive sensitization signature and classification trees identified statistical thresholds to predict sensitizer potency. The SVM computed 91% tri-culture prediction accuracy using the top 3 ranking biomarkers (IL-8, MIP-1β, and GM-CSF) and improved the detection of pre- and pro-haptens. This assay combined with data analysis presents a promising approach and offers the possibility of multi-metric analysis for enhanced ACD sensitizer screening.

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