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Approaches to incorporate extracellular vesicles into exposure science, toxicology, and public health research

Journal of Exposure Science & Environmental Epidemiology volume 32, pages 647–659 (2022)Cite this article

Abstract

Extracellular vesicles (EVs) represent small, membrane-enclosed particles that are derived from parent cells and are secreted into the extracellular space. Once secreted, EVs can then travel and communicate with nearby or distant cells. Due to their inherent stability and biocompatibility, these particles can effectively transfer RNAs, proteins, and chemicals/metabolites from parent cells to target cells, impacting cellular and pathological processes. EVs have been shown to respond to disease-causing agents and impact target cells. Given that disease-causing agents span environmental contaminants, pathogens, social stressors, drugs, and other agents, the translation of EV methods into public health is now a critical research gap. This paper reviews approaches to translate EVs into exposure science, toxicology, and public health applications, highlighting blood as an example due to its common use within clinical, epidemiological, and toxicological studies. Approaches are reviewed surrounding the isolation and characterization of EVs and molecular markers that can be used to inform EV cell-of-origin. Molecular cargo contained within EVs are then discussed, including an original analysis of blood EV data from Vesiclepedia. Methods to evaluate functional consequences and target tissues of EVs are also reviewed. Lastly, the expanded integration of these approaches into future public health applications is discussed, including the use of EVs as promising biomarkers of exposure, effect, and disease.

Impact statement

  • Extracellular vesicles (EVs) represent small, cell-derived structures consisting of molecules that can serve as biomarkers of exposure, effect, and disease.

  • This review lays a novel foundation for integrating EVs, a rapidly advancing molecular biological tool, into the field of public health research including epidemiological, toxicological, and clinical investigations.

  • This article represents an important advancement in public health and exposure science as it is among the first to translate EVs into this field.

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Fig. 1: Mechanisms of EV biogenesis, resulting in three defined classes of EVs (i.e., exosomes, microvesicles, and apoptotic bodies) with overlapping ranges in size, composition, and function.
Fig. 2: The most common proteins that have been measured in EVs circulating in human blood and their related biological functions.
Fig. 3: The most common lipids, mRNAs, and miRNAs and that have been measured in EVs circulating in human blood.
Fig. 4: Overview of example utilities of EV research in environmental science, toxicology, and public health applications.

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Funding

This study was supported by grants from the National Institutes of Health (NIH) from the National Institute of Environmental Health Sciences (1R21ES031740, P42ES031007). Support was additionally provided through the Institute for Environmental Health Solutions (IEHS) at the University of North Carolina Gillings School of Global Public Health.

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Authors and Affiliations

  1. Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Celeste K. Carberry, Alexis Payton & Julia E. Rager

  2. The Institute for Environmental Health Solutions, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Celeste K. Carberry, Deepak Keshava, Alexis Payton & Julia E. Rager

  3. Curriculum in Toxicology and Environmental Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC, USA

    Gregory J. Smith & Julia E. Rager

  4. Department of Genetics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA

    Gregory J. Smith

Authors
  1. Celeste K. Carberry
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  2. Deepak Keshava
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  3. Alexis Payton
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  4. Gregory J. Smith
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  5. Julia E. Rager
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Contributions

CKC, DK, and JER were responsible for reviewing available literature and drafting review text. AP was responsible for extracting and analyzing extracellular vesicle molecular data. CKC and AP were responsible for manuscript visualizations. GJS and JER were responsible for reviewing overall content and providing feedback.

Corresponding author

Correspondence to Julia E. Rager.

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Carberry, C.K., Keshava, D., Payton, A. et al. Approaches to incorporate extracellular vesicles into exposure science, toxicology, and public health research. J Expo Sci Environ Epidemiol 32, 647–659 (2022). https://doi.org/10.1038/s41370-022-00417-w

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  • DOI: https://doi.org/10.1038/s41370-022-00417-w

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