John W. Ludlow, Alexander Kinev, Michael VanKanegan, Ben Buehrer, Nick Trotta, and Joydeep Basu
There is an unmet need in toxicological risk assessment for direct estimation of both the magnitude and variability of human responses to environmental toxicants. Toxicological assays currently rely on a range of cell lines and in vivo models, as well as cell viability and proliferation. In this chapter, we explore using a primary human stem/progenitor cells for development of a quantitative, high content imaging-based assay not only for environmental agent-induced cell death, but also for differentiation disruption. We will address four challenges relevant to toxicological risk assessment practice by discussing an assay platform that is: (1) amenable to a high-throughput format, (2) applicable to studying the effects of toxicants on cell differentiation, (3) sensitive to low doses of environmental hazards that are relevant to human exposure, and (4) can be used for direct estimation of the variability of responses in human population.