Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Direct isolation of circulating extracellular vesicles from blood for vascular risk profiling in type 2 diabetes mellitus
Ist Teil von
Lab on a chip, 2021-06, Vol.21 (13), p.2511-2523
Ort / Verlag
Cambridge: Royal Society of Chemistry
Erscheinungsjahr
2021
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
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.
A simple, economical and scalable microfluidic separation technology (ExoDFF) for label-free isolation of circulating extracellular vesicles (EVs) from whole blood.