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Direct isolation of circulating extracellular vesicles from blood for vascular risk profiling in type 2 diabetes mellitus

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Abstract

Extracellular vesicles (EVs) are key mediators of communication among cells, and clinical utilities of EVs-based biomarkers remain limited due to difficulties in isolating EVs from whole blood reliably. We report a novel inertial-based microfluidic platform for direct isolation of nanoscale EVs (exosomes, 50 to 200 nm) and medium-sized EVs (microvesicles, 200 nm to 1 μm) from blood with high efficiency (three-fold increase in EV yield compared to ultracentrifugation). In a pilot clinical study of healthy (n = 5) and type 2 diabetes mellitus (T2DM, n = 9) subjects, we detected higher EV levels in T2DM patients (P < 0.05), and identified a subset of “high-risk” T2DM subjects with abnormally high (∼10-fold to 50-fold) amounts of platelet (CD41a+) or leukocyte-derived (CD45+) EVs. Our in vitro endothelial cell assay further revealed that EVs from “high-risk” T2DM subjects induced significantly higher vascular inflammation (ICAM-1 expression) (P < 0.05) as compared to healthy and non-“high-risk” T2DM subjects, reflecting a pro-inflammatory phenotype. Overall, the EV isolation tool is scalable, and requires less manual labour, cost and processing time. This enables further development of EV-based diagnostics, whereby a combined immunological and functional phenotyping strategy can potentially be used for rapid vascular risk stratification in T2DM.

Graphical abstract: Direct isolation of circulating extracellular vesicles from blood for vascular risk profiling in type 2 diabetes mellitus

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Supplementary files

Article information


Submitted
16 Apr 2021
Accepted
23 May 2021
First published
24 May 2021

Lab Chip, 2021, Advance Article
Article type
Paper

Direct isolation of circulating extracellular vesicles from blood for vascular risk profiling in type 2 diabetes mellitus

H. M. Tay, S. Y. Leong, X. Xu, F. Kong, M. Upadya, R. Dalan, C. Y. Tay, M. Dao, S. Suresh and H. W. Hou, Lab Chip, 2021, Advance Article , DOI: 10.1039/D1LC00333J

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