LABELING EXTRACELLULAR VESICLES FOR HIGHLY SENSITIVE FLOW CYTOMETRY ANALYSES

Extracellular vesicles (EVs) are released by shedding during many different processes by all cell types. They cross all biological barriers and have been detected in all body fluids. For these reasons EVs are increasingly thought to be new potential dynamic biomarkers useful for liquid biopsy. Howe...

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Language:English
Published: PAGEPress Publications 2025-08-01
Series:European Journal of Histochemistry
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Online Access:https://www.ejh.it/ejh/article/view/4302
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description Extracellular vesicles (EVs) are released by shedding during many different processes by all cell types. They cross all biological barriers and have been detected in all body fluids. For these reasons EVs are increasingly thought to be new potential dynamic biomarkers useful for liquid biopsy. However, the application of pre-analytical processing phases before any EV flow cytometry measurement is mandatory, even if their impact on results is not predictable. For this reason, the translation of basic research into clinical practice has been precluded. We have optimized a simple flow cytometry method, which, avoiding any pre-enrichment step, allows the identification, classification, enumeration, and separation, by fluorescence activated cell sorting, circulating EVs stemming from different parental cells. This protocol takes advantage of a lipophilic cationic dye (LCD) able to probe EVs, which has been combined with fluorescent phalloidin to exclude damaged elements and different mixes of specific monoclonal antibodies. The application of the newly optimized PFC protocol here described allowed the obtainment of repeatable EVs counts. The translation of this PFC protocol to fluorescence-activated cell sorting allowed us to separate EVs from fresh peripheral blood samples and many others biological fluids, as well as cell supernatants. Sorted EVs preparations resulted particularly suitable for proteomic analyses, which we applied to study their protein cargo, as well as for in vitro and in vivo functional assays. Therefore, LCD staining of EVs may open new routes for the EV clinical translation.
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issn 1121-760X
2038-8306
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series European Journal of Histochemistry
spelling doaj-art-342c6410fa03406bbe166c094b9e1e592025-08-23T11:19:33ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062025-08-0169s210.4081/ejh.2025.4302LABELING EXTRACELLULAR VESICLES FOR HIGHLY SENSITIVE FLOW CYTOMETRY ANALYSES Extracellular vesicles (EVs) are released by shedding during many different processes by all cell types. They cross all biological barriers and have been detected in all body fluids. For these reasons EVs are increasingly thought to be new potential dynamic biomarkers useful for liquid biopsy. However, the application of pre-analytical processing phases before any EV flow cytometry measurement is mandatory, even if their impact on results is not predictable. For this reason, the translation of basic research into clinical practice has been precluded. We have optimized a simple flow cytometry method, which, avoiding any pre-enrichment step, allows the identification, classification, enumeration, and separation, by fluorescence activated cell sorting, circulating EVs stemming from different parental cells. This protocol takes advantage of a lipophilic cationic dye (LCD) able to probe EVs, which has been combined with fluorescent phalloidin to exclude damaged elements and different mixes of specific monoclonal antibodies. The application of the newly optimized PFC protocol here described allowed the obtainment of repeatable EVs counts. The translation of this PFC protocol to fluorescence-activated cell sorting allowed us to separate EVs from fresh peripheral blood samples and many others biological fluids, as well as cell supernatants. Sorted EVs preparations resulted particularly suitable for proteomic analyses, which we applied to study their protein cargo, as well as for in vitro and in vivo functional assays. Therefore, LCD staining of EVs may open new routes for the EV clinical translation. https://www.ejh.it/ejh/article/view/4302WORKSHOP: NEW HORIZONS IN FLOW CYTOMETRY: ADVANCES IN ANALYSES AND CHARACTERIZATION OF EXTRACELLULAR VESICLES
spellingShingle LABELING EXTRACELLULAR VESICLES FOR HIGHLY SENSITIVE FLOW CYTOMETRY ANALYSES
European Journal of Histochemistry
WORKSHOP: NEW HORIZONS IN FLOW CYTOMETRY: ADVANCES IN ANALYSES AND CHARACTERIZATION OF EXTRACELLULAR VESICLES
title LABELING EXTRACELLULAR VESICLES FOR HIGHLY SENSITIVE FLOW CYTOMETRY ANALYSES
title_full LABELING EXTRACELLULAR VESICLES FOR HIGHLY SENSITIVE FLOW CYTOMETRY ANALYSES
title_fullStr LABELING EXTRACELLULAR VESICLES FOR HIGHLY SENSITIVE FLOW CYTOMETRY ANALYSES
title_full_unstemmed LABELING EXTRACELLULAR VESICLES FOR HIGHLY SENSITIVE FLOW CYTOMETRY ANALYSES
title_short LABELING EXTRACELLULAR VESICLES FOR HIGHLY SENSITIVE FLOW CYTOMETRY ANALYSES
title_sort labeling extracellular vesicles for highly sensitive flow cytometry analyses
topic WORKSHOP: NEW HORIZONS IN FLOW CYTOMETRY: ADVANCES IN ANALYSES AND CHARACTERIZATION OF EXTRACELLULAR VESICLES
url https://www.ejh.it/ejh/article/view/4302