Work

Omics-Based Platform for Studying Chemical Toxicity Using Stem Cells

Year: 2017

Type: article

Abstract: The new strategy for chemical toxicity testing and modeling is to use in vitro human cell-based assays in conjunction with quantitative high-throughput screening (qHTS) technology, to identify molecular mechanisms and predict in vivo responses. Stem cells are more physiologically relevant than immortalized cell lines because of their unique proliferation and differentiation potentials. We established a robust two stem cells-two lineages assay system, encompassing human mesenchymal stem cells (hMSCs) along osteogenesis and human induced pluripotent stem cells (hiPSCs) along hepatogenesis. We performed qHTS phenotypic screening of LOPAC1280 and identified 38 preliminary hits for hMSCs. This was followed by validation of a selected number of hits and determination of their IC 50 values and mechanistic studies of idarubicin and cantharidin treatments using proteomics and bioinformatics. In general, hiPSCs were more sensitive than hMSCs to chemicals, and differentiated progenies were less sensitive than their progenitors. We showed that chemical toxicity depends on both stem cell types and their differentiation stages. Proteomics identified and quantified over 3000 proteins for both stem cells. Bioinformatics identified apoptosis and G2/M as the top pathways conferring idarubicin toxicity. Our Omics-based assays of stem cells provide mechanistic insights into chemical toxicity and may help prioritize chemicals for in-depth toxicological evaluations.

Source: Journal of Proteome Research

DOI: 10.1021/acs.jproteome.7b00693

Authors: Yan Han, Jinghua Zhao, Ruili Huang, Menghang Xia, Daojing Wang

Institutions: Newomics (United States), National Institutes of Health, National Center for Advancing Translational Sciences

Language: English

Topic: Animal testing and alternatives

Subfield: Small Animals

Field: Veterinary

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green