Citation:

Schwab, A. AND S. Hunter. Human neurovascular unit on a chip for assessing thyroid hormone mediated neurodevelopment. Future Tox IV, Arlington, Virginia, November 14 - 16, 2018.

Impact/Purpose:

Abstract for poster presentation at SOT IV

Description:

The ability to model human brain and blood-brain barrier development in vitro is a critical biotechnical advancement, which could strengthen developmental neurotoxicity testing. Here we focus on the development of the early human nervous system in a neurovascular unit (NVU) model using a dynamic (ibidi 2-compartment microfluidic slide) and a static (24-well transwell) model system comprised of endothelial, pericyte, and neural progenitor cells. We demonstrate low permeability across the NVU/blood-brain barrier as well as glio- and neuro-genesis of EZ Sphere stem cell-derived neural progenitors. Both dynamic and static model systems have been analyzed with automated high-content imaging allowing for robust, non-biased measurements of neural differentiation and neurite outgrowth which are crucial for future toxicity testing. Future studies to evaluate the morphological effects of thyroid hormone disrupting chemicals will allow a determination of the consequences of hypothyroidism or TH signaling disruption during brain development. Combined, these novel, complementary human NVU model systems will be useful in understanding the consequences of chemical effects or physiological dysregulation on early neurodevelopment periods and contribute to understanding the mechanisms underlying neurodevelopmental disorders. Ultimately, the information gained using these advanced model systems may have a profound effect on advancing neurotoxicity research. This abstract does not represent EPA policy.

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