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

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.

Wildfires and extracellular vesicles: Exosomal MicroRNAs as mediators of cross-tissue cardiopulmonary responses to biomass smoke

“…NTA demonstrated particle diameters between an average of 120 and 150 nm ( Table A.4 , Fig. A.2A ), within range of the EV subtype of exosomes ( Carberry et al 2022 ). The overall particle charge was between −18.10 and −12.01 mV ( Table A.4 , Fig.…”

“…We recognize that further evaluation of this mechanism is needed, where the field of EV research within environmental health / toxicology is just now emerging ( Carberry et al 2022 ). In this study, for example, it is difficult to elucidate what specific event(s) impacted plasma EV miRNA composition.…”

“…There is notably a lack of specific markers that can effectively differentiate between EV subtypes ( Thery et al 2018 ). EV subtypes also overlap in size, with diameters ranging between 30 and 200 nm for exosomes, 100–2000 nm for microvesicles, and 1000–5000 nm for apoptotic bodies ( Carberry et al 2022 ). Therefore, the MISEV2018 advocates for the overall reporting of detected size range, as opposed to using size information to make author-dependent conclusions on EV subtypes.…”

“…Effects include the alteration of target cell gene/protein expression which can impact molecular pathways influencing cellular phenotypes, biological functions, and overall tissue pathology. The specific content of EVs depend on their cell of origin, but generally contain nucleic acids, proteins, amino acids, lipids, and metabolites, which remain functional and may be transferred to target cells ( Carberry et al 2022 ; Fu et al 2020 ; Zhang et al 2017 ).…”

“…EV-based therapies are even being proposed for the prevention/treatment of cardiovascular disease, as evaluated based on blood delivery mechanisms; though there are notable concerns regarding side effects on other tissues ( Davidson et al 2019 ). In terms of environmental exposures, it is clear that the investigation of EVs will help to elucidate important intercellular communication mechanisms and associated disease etiologies relevant to public health ( Carberry et al 2022 ).…”