Comparison of Methods for Isolation and Characterization of Total and Astrocyte‐Enriched Extracellular Vesicles From Human Serum and Plasma

ABSTRACT Extracellular vesicles (EV) which play critical roles in intercellular communication, have garnered interest as biomarkers with researchers studying brain‐related disease processes due to their ability to be isolated from various biofluids. Astrocytes, a type of glial cell, play a critical...

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Main Authors: Leandra K. Figueroa‐Hall, Kaiping Burrows, Ahlam M. Alarbi, Bethany N. Hannafon, Cole Hladik, Chibing Tan, Rajagopal Ramesh, Jennifer L. Stewart, Victoria B. Risbrough, Martin P. Paulus, T. Kent Teague
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:Journal of Extracellular Biology
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Online Access:https://doi.org/10.1002/jex2.70035
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author Leandra K. Figueroa‐Hall
Kaiping Burrows
Ahlam M. Alarbi
Bethany N. Hannafon
Cole Hladik
Chibing Tan
Rajagopal Ramesh
Jennifer L. Stewart
Victoria B. Risbrough
Martin P. Paulus
T. Kent Teague
author_facet Leandra K. Figueroa‐Hall
Kaiping Burrows
Ahlam M. Alarbi
Bethany N. Hannafon
Cole Hladik
Chibing Tan
Rajagopal Ramesh
Jennifer L. Stewart
Victoria B. Risbrough
Martin P. Paulus
T. Kent Teague
author_sort Leandra K. Figueroa‐Hall
collection DOAJ
description ABSTRACT Extracellular vesicles (EV) which play critical roles in intercellular communication, have garnered interest as biomarkers with researchers studying brain‐related disease processes due to their ability to be isolated from various biofluids. Astrocytes, a type of glial cell, play a critical role in neuronal regulation and function. As such, EV enriched from astrocytes can be used to interrogate cargo and identify mechanisms by which astrocytes communicate with other cells of the central nervous system or shed light on pathophysiological conditions. This manuscript compared five EV isolation methods (differential ultracentrifugation [dUC], precipitation, precipitation + purification, silicon carbon resin and size exclusion chromatography [SEC]) using small volumes of human plasma and serum with a focus on immunocapture of astrocyte‐enriched EV (AEEV), with the excitatory amino acid transporter 1, or GLAST. Methods were evaluated on yield, purity, recovery and downstream application to include immunoassays for tetraspanin, immune and astrocyte markers. Results revealed that whilst precipitation‐based methods such as ExoQuick yielded higher EV concentrations, size exclusion (SmartSEC, qEV) provided greater purity, emphasizing a trade‐off between yield and purity. This study provides a comprehensive resource for researchers in selecting EV isolation methods tailored to small biobanked clinical samples, with the goal of advancing biomarker discovery in Neuroscience.
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spelling doaj-art-d1b90894a8964d9ab1dcb70f581fb5d42025-08-20T02:45:04ZengWileyJournal of Extracellular Biology2768-28112025-02-0142n/an/a10.1002/jex2.70035Comparison of Methods for Isolation and Characterization of Total and Astrocyte‐Enriched Extracellular Vesicles From Human Serum and PlasmaLeandra K. Figueroa‐Hall0Kaiping Burrows1Ahlam M. Alarbi2Bethany N. Hannafon3Cole Hladik4Chibing Tan5Rajagopal Ramesh6Jennifer L. Stewart7Victoria B. Risbrough8Martin P. Paulus9T. Kent Teague10Laureate Institute for Brain Research Tulsa Oklahoma USALaureate Institute for Brain Research Tulsa Oklahoma USAIntegrative Immunology Center University of Oklahoma (OU) Tulsa Oklahoma USADepartment of Obstetrics and Gynecology OU Health Sciences Center (OUHSC) Oklahoma City Oklahoma USADepartment of Obstetrics and Gynecology OU Health Sciences Center (OUHSC) Oklahoma City Oklahoma USAIntegrative Immunology Center University of Oklahoma (OU) Tulsa Oklahoma USAOU Health Stephenson Cancer Center Oklahoma City Oklahoma USALaureate Institute for Brain Research Tulsa Oklahoma USAVA Center of Excellence for Stress and Mental Health La Jolla California USALaureate Institute for Brain Research Tulsa Oklahoma USAIntegrative Immunology Center University of Oklahoma (OU) Tulsa Oklahoma USAABSTRACT Extracellular vesicles (EV) which play critical roles in intercellular communication, have garnered interest as biomarkers with researchers studying brain‐related disease processes due to their ability to be isolated from various biofluids. Astrocytes, a type of glial cell, play a critical role in neuronal regulation and function. As such, EV enriched from astrocytes can be used to interrogate cargo and identify mechanisms by which astrocytes communicate with other cells of the central nervous system or shed light on pathophysiological conditions. This manuscript compared five EV isolation methods (differential ultracentrifugation [dUC], precipitation, precipitation + purification, silicon carbon resin and size exclusion chromatography [SEC]) using small volumes of human plasma and serum with a focus on immunocapture of astrocyte‐enriched EV (AEEV), with the excitatory amino acid transporter 1, or GLAST. Methods were evaluated on yield, purity, recovery and downstream application to include immunoassays for tetraspanin, immune and astrocyte markers. Results revealed that whilst precipitation‐based methods such as ExoQuick yielded higher EV concentrations, size exclusion (SmartSEC, qEV) provided greater purity, emphasizing a trade‐off between yield and purity. This study provides a comprehensive resource for researchers in selecting EV isolation methods tailored to small biobanked clinical samples, with the goal of advancing biomarker discovery in Neuroscience.https://doi.org/10.1002/jex2.70035astrocyte‐enriched extracellular vesiclesdifferential centrifugationextracellular vesiclesprecipitationprecipitation + purificationresin‐separating matrix
spellingShingle Leandra K. Figueroa‐Hall
Kaiping Burrows
Ahlam M. Alarbi
Bethany N. Hannafon
Cole Hladik
Chibing Tan
Rajagopal Ramesh
Jennifer L. Stewart
Victoria B. Risbrough
Martin P. Paulus
T. Kent Teague
Comparison of Methods for Isolation and Characterization of Total and Astrocyte‐Enriched Extracellular Vesicles From Human Serum and Plasma
Journal of Extracellular Biology
astrocyte‐enriched extracellular vesicles
differential centrifugation
extracellular vesicles
precipitation
precipitation + purification
resin‐separating matrix
title Comparison of Methods for Isolation and Characterization of Total and Astrocyte‐Enriched Extracellular Vesicles From Human Serum and Plasma
title_full Comparison of Methods for Isolation and Characterization of Total and Astrocyte‐Enriched Extracellular Vesicles From Human Serum and Plasma
title_fullStr Comparison of Methods for Isolation and Characterization of Total and Astrocyte‐Enriched Extracellular Vesicles From Human Serum and Plasma
title_full_unstemmed Comparison of Methods for Isolation and Characterization of Total and Astrocyte‐Enriched Extracellular Vesicles From Human Serum and Plasma
title_short Comparison of Methods for Isolation and Characterization of Total and Astrocyte‐Enriched Extracellular Vesicles From Human Serum and Plasma
title_sort comparison of methods for isolation and characterization of total and astrocyte enriched extracellular vesicles from human serum and plasma
topic astrocyte‐enriched extracellular vesicles
differential centrifugation
extracellular vesicles
precipitation
precipitation + purification
resin‐separating matrix
url https://doi.org/10.1002/jex2.70035
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