Organs-on-a-Chip: The Future of Chemical Toxicity Testing

By Tom Knudsen, Ph.D.

Illustration of a human brain on a computer chipLast week, my colleague Jim Johnson shared a blog post (Exciting Times for Toxicology: Creating New Predictive Models) about EPA’s leadership role to advance chemical toxicity research, including news that the Agency’s Science to Achieve Results (STAR) grant program will provide research institutions with up to $6 million each to further develop organotypic culture models (OCMs)—“organ-on-a-chip” microsystems. The grants support innovative research that will eventually model complex functions of the human system like metabolism, multicellular communication within a tissue or target organ, and how these multiscale systems change over time.

Today, I am excited to share the three institutions that will receive EPA support to advance this innovative work. The institutions and their work are highlighted below.

  • University of Wisconsin, Madison – Human Model Analysis of Pathways Center:
    The Center will research innovative cellular modeling methods to develop a broadly applicable set of tools for toxicity screening. Researchers will develop OCMs for functions within the liver, central nervous system and mammary gland with invasive carcinoma.
  • Vanderbilt University Resource for Organotypic Models for Predictive Toxicology:
    The Center will advance alternative methods of chemical toxicity testing using 3D cultures of tissues to reduce uncertainties regarding specific chemical exposures. The models will simulate a more accurate response in the liver, mammary gland, limb/joint formation, and placental tissues under different conditions and stressors.
  • University of Washington – Predictive Toxicology Center for Organotypic Cultures and Assessment of AOPs for Engineered Nanomaterials:
    The Center will develop innovative OCMs to evaluate potential toxicity in cells and organs following exposure to metal-based engineered nanomaterials within an adverse outcome pathway (AOP) model. The research will target airway tissues, kidney, liver, and testis. Models will also factor in lifestage and genetic background.

We believe that the “organ-on-a-chip” microsystems and models the centers develop will provide vital information to predict toxicity and chemical exposure within the human body and at different lifestages and provide data that further minimizes the lengthy testing involved with animal studies. Organotypic culture models have the potential to improve, evaluate, and extend computational models that are currently under development by our own scientists.

Research data will not only help explain how organs and tissues respond to various chemicals, but these models will ultimately be used to validate other predictive models such as EPA’s virtual embryo models which will advance our understanding of the potential links between chemical exposure and development, disease, or other responses.

For more information on OCM Research and our STAR grants, please see our fact sheet.

About the Author: Tom Knudsen, Ph.D. is a developmental systems biologist at EPA’s Center for Computational Toxicology. His research focuses on predictive models of developmental toxicity—building and testing sophisticated computer models. In addition to his research at EPA, Dr. Knudsen is an Adjunct Professor at the University of Louisville, Editor-in-Chief of the scientific journal Reproductive Toxicology, and Past-President of the Teratology Society. Read more about him and his work.





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