Cell-Based Microvascular Toxicology
From In Utero to Old Age:
Lifelong Exposure to Environmental Toxicants
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Environmental toxicants are all around us — from the air we breathe to the products we use daily. Over a lifetime, this exposure can contribute to the development of serious health conditions, including cardiovascular disease (CVD), the leading cause of death globally.
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Why Do Some People Get Sick While Others Don’t?
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Not everyone responds to toxicants in the same way. Sensitivity can vary based on:
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Genetics
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Existing health conditions
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Nutrition
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Sex and age
Understanding how individuals respond to specific chemicals is critical to preventing disease and personalizing treatment. That’s where our science comes in.
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Our Solution: Testing Sensitivity Using Your Own Cells
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At the core of our platform is a specialized type of blood-derived progenitor cell called Endothelial Colony-Forming Cells (ECFCs). These cells play a vital role in repairing blood vessels and supporting cardiovascular health.
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We isolate ECFCs from a person’s blood sample and test their response to drugs and environmental toxicants in vitro. If these cells show signs of dysfunction, it may signal a higher risk for vascular damage and related health issues in the individual.
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Why ECFCs Matter
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Personalized insight: Detect early signs of toxicant sensitivity unique to each person
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Non-invasive sampling: Cells come from a standard blood draw
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Predictive value: Potential to forecast cardiovascular vulnerability before symptoms appear
Publications
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
Abstract
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
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Abstract
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.