Emerging methods in biomarker identification for extracellular vesicle‐based liquid biopsy

Abstract

Extracellular vesicles (EVs) are released by many cell types and distributed within various biofluids. EVs have a lipid membrane-confined structure that allows for carrying unique molecular information originating from their parent cells. The species and quantity of EV cargo molecules, including nucleic acids, proteins, lipids, and metabolites, may vary largely owing to their parent cell types and the pathophysiologic status. Such heterogeneity in EV populations provides immense challenges to researchers, yet allows for the possibility to prognosticate the pathogenesis of a particular tissue from unique molecular signatures of dispersing EVs within biofluids. However, the inherent nature of EV's small size requires advanced methods for EV purification and evaluation from the complex biofluid. Recently, the interdisciplinary significance of EV research has attracted growing interests, and the EV analytical platforms for their diagnostic prospect have markedly progressed. This review summarizes the recent advances in these EV detection techniques and methods with the intention of translating an EV-based liquid biopsy into clinical practice. This article aims to present an overview of current EV assessment techniques, with a focus on their progress and limitations, as well as an outlook on the clinical translation of an EV-based liquid biopsy that may augment current paradigms for the diagnosis, prognosis, and monitoring the response to therapy in a variety of disease settings.

A simple immunoassay for extracellular vesicle liquid biopsy in microliters of non-processed plasma

“…Multiple candidate EV biomarkers have been suggested for different pathologies, however, for a routine translation into the clinics, high throughput comparative studies are still necessary to define the suitability of each particular biomarker in a given disease context. Such association studies, requiring the analysis of samples from large patient cohorts, are hampered by currently available methods which require either relatively large sample volumes or long protocols of nanovesicle pre-enrichment together with the use of sophisticated equipment or specialised personnel [ 10 – 13 ]. The development of nanosensors makes possible to specifically detect EVs using small sample volumes from large numbers of patients [ 14 – 16 ], but these new technologies require purpose-designed devices assembled in specialised laboratories and, data derived from this type of study are still scarce.…”

Comparison of Curative Effect of Human Umbilical Cord-Derived Mesenchymal Stem Cells and Their Small Extracellular Vesicles in Treating Osteoarthritis

“…This phenomenon results from the inherent heterogeneity of sEVs and the lack of separation standard. 66 , 67 Thus, we need to determine the optimal dosage of therapeutic sEVs on the basis of specific conditions or diseases for promoting clinical translation. In addition, the safety and effectiveness concerns of sEVs administration must be methodically addressed in large animals.…”

Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA

“…However, pure exosomes cannot be obtained by ultracentrifugation alone, and accordingly, it would be more appropriate to call them small EVs. To solve this problem, distinct surface markers can distinguish exosomes from other types of EVs [143].…”