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Development of an In Vitro Human Thyroid Microtissue Model for Chemical Screening.

Chad Deisenroth1, Valerie Y Soldatow2, Jermaine Ford3

  • 1National Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|December 7, 2019
PubMed
Summary
This summary is machine-generated.

This study developed a 3D human thyroid microtissue model to accurately assess thyroid disrupting chemicals (TDCs). The new model successfully restored thyroid hormone synthesis, aiding TDC hazard identification.

Keywords:
endocrine toxicologyorganotypic culture modelthyroidthyroid disrupting chemicals

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Area of Science:

  • Endocrinology
  • Toxicology
  • Cell Biology

Background:

  • Thyroid hormones (TH) regulate critical physiological processes.
  • The US EPA Endocrine Disruptor Screening Program (EDSP) uses high-throughput screening (HTS) to identify potential thyroid disrupting chemicals (TDCs).
  • Data gaps exist regarding the specificity and in vivo relevance of HTS findings for TDCs.

Purpose of the Study:

  • To develop a medium-throughput organotypic screening assay using reconstructed human thyroid microtissues.
  • To quantitatively evaluate the disruptive effects of chemicals on thyroid hormone (TH) production and secretion.
  • To compare 2D and 3D culture formats for modeling human thyroid cells.

Main Methods:

  • Primary human thyroid cells were cultured in 2D and 3D formats.
  • Cellular morphology, gene expression, thyroglobulin (TG) production, and TH synthesis were analyzed over 20 days.
  • High-content image analysis verified follicular epithelial cell markers (NKX2-1, KRT7, TG).

Main Results:

  • The 3D microtissue model restored TH synthesis, unlike the 2D model.
  • The 3D format demonstrated inhibition of TH synthesis using known thyroid disrupting chemicals.
  • The assay successfully characterized thyroid cell function and response to chemical disruption.

Conclusions:

  • A 3D human thyroid microtissue assay can effectively model TH synthesis and disruption.
  • This assay provides a valuable tool for interpreting HTS results for TDCs.
  • The developed assay aids in hazard identification of potential thyroid disrupting chemicals.