Origins to Outcomes: A Role for Extracellular Vesicles in Precision Medicine

Abstract

Extracellular vesicles (EVs) are of great interest in biological research, and though they are a relatively recent discovery, they have rapidly shown great potential for use in clinical applications. The various techniques used in EV isolation along with their respective strengths, weaknesses, and potential for downstream applications are outlined here. A brief description of the different approaches in exosome characterisation are subsequently described. It has been highlighted that despite the recent developments in these processes, there is still a great deal of refinement to be made. EVs are produced by almost all cell types, found in many biological samples, and are implicated in multiple biological processes including cargo trafficking, cell-cell communication, and signal transduction. The presence of these EVs and their varied cargo in a biological sample can be indicative in disease diagnosis, and guide precision medicine-based approaches to disease management. EVs have been reported to actin the benefit of the cell through moderating repair and regeneration, but they can also act to the detriment of the cell through increased tumorigenesis and metastasis. This duality is intriguing as it can allow for the use of EVs in distinct therapeuticapproaches and displays their versatility in potential downstream applications. In this review, examples of the cellular roles of EVs and their applications in pathological and regenerative contexts are explored. In reviewing some of the developments madein recent times, EVs are shown to be very promising both in diagnostic and therapeutic approaches.

Measuring particle concentration of multimodal synthetic reference materials and extracellular vesicles with orthogonal techniques: Who is up to the challenge?

“…Additionally, the lack of highly repeatable standard protocols for the measurements of all critical sample attributes, combined with the lack of reference materials are also impacting the reproducibility of EV characterization within acceptable industrial confidence variance. Such lack of fundamental knowledge is probably slowing down both the basic research and the regulatory approval process in this area, as reported by some of the authors previous works (Gioria et al, 2018;Hole et al, 2013;Savage et al, 2018). While attempting to provide clear answers to the EV community in term of reproducibility, accuracy and acceptability, this work is focussed on an in-depth analysis of the key EV isolate quality attributes: concentration and size distribution.…”

“…EVs can be subclassified into several different subsets based on biogenesis (Akers et al., 2013; Théry et al., 2018), in order of increasing size, such as exosomes (< 150 nm), microvesicles (> 100 nm) and apoptotic bodies (> 100 nm) (Hessvik & Llorente, 2018). EVs have been considered a recent avenue for biomedical investigation in both regenerative and pathogenic contexts, with potential in diagnostic and therapeutic applications (Savage et al., 2018). Their potential use in manifold applications, including drug delivery, particle loading and other theragnostic applications have been reviewed recently (Piffoux et al., 2018).…”

“…This study compares single‐particle interferometric reflectance imaging sensing (SP‐IRIS), NTA, fluorescence, microfluidic resistive pulse sensing (MRPS) and nanoflow cytometry (nFCM, NanoFCM) for particle concentration measurements. This work, and many others within the EV community are stressing the importance of phenotyping and EV biomarking as additional tools to be taken into consideration for quality control of EV sample source and purity in addition to concentration measurements (Clogston et al., 2020; Savage et al., 2018; Tian et al., 2018; Vogel et al., 2016). It is important to stress that the absence of reproducibility in the quality of EV samples, has too often limited comparability of results in characterization trials.…”