We develop an assay platform to assess an impairment of Endothelial-Colony Forming Cells (ECFC) in response to drugs and environmental toxicants. As progenitor cells, ECFC are required to maintain cardiovascular health. ECFC can be isolated from a person’s blood and tested in vitro. Their impairment may indicate potential vulnerability of a donor to a particular drug or a toxicant.
From In Utero to an Old Age People Are Exposed to Environmental Toxicants
Exposure to Toxicants Has Been Linked to Developement of Cardiovascular Disease (CVD) - #1 Cause of Death
To Reduce CVD Burden, It Is Necessary to Assess Population-Wide Chemical Toxicity
Testing ECFC response to metabolic regulators and environmental toxicants. Dose-response curves to 9 substances were obtained using 384 well plate. Cells were plated in triplicates and after overnight incubation, titers of chemicals were added to wells. Cells were grown for additional 48 hrs and stained with a vital dye 5-Carboxyfluorescein diacetate.
Cord Blood Cells for Developmental Toxicology and Environmental Health Front Public Health. 2015 Dec 3;3:265. doi: 10.3389/fpubh.2015.00265. eCollection 2015.
Dora Il’yasova, Noreen Kloc, and Alexander Kinev
The Tox21 program initiated a shift in toxicology toward in vitro testing with a focus on the biological mechanisms responsible for toxicological response. We discuss the applications of these initiatives to developmental toxicology. Specifically, we briefly review current approaches that are widely used in developmental toxicology to demonstrate the gap in relevance to human populations. An important aspect of human relevance is the wide variability of cellular responses to toxicants. We discuss how this gap can be addressed by using cells isolated from umbilical cord blood, an entirely non-invasive source of fetal/newborn cells. Extension of toxicological testing to collections of human fetal/newborn cells would be useful for better understanding the effect of toxicants on fetal development in human populations. By presenting this perspective, we aim to initiate a discussion about the use of cord blood donor-specific cells to capture the variability of cellular toxicological responses during this vulnerable stage of human development.
Toxicological Risk Assessment – Proposed Assay Platform Using Stem and Progenitor Cell Differentiation in Response to Environmental Toxicants. Issues in Toxicology No. 29. Human Stem Cell Toxicology. Edited by James L. Sherley. The Royal Society of Chemistry 2016. Published by the Royal Society of Chemistry.
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.