Assessment of technical and clinical utility of a bead-based flow cytometry platform for multiparametric phenotyping of CNS-derived extracellular vesicles
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Alexandra Brahmer
- Carsten Geiss
- Andriani Lygeraki
- Elmo Neuberger
- Theophilos Tzaridis
- Tinh Thi Nguyen
- Felix Luessi
- Anne Regnier-Vigouroux
- Gunther Hartmann
- Perikles Simon
- Kristina Endres
- Stefan Bittner
- Katrin S Reiners
- Eva-Maria Kraemer-Albers
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001079288500001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1186/s12964-023-01308-9
- eISSN
- 1478-811X
- Externe Identifier
- Clarivate Analytics Document Solution ID: T6TL1
- PubMed Identifier: 37803478
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- CELL COMMUNICATION AND SIGNALING
- Schlüsselwörter
- Extracellular vesicles
- CNS diseases
- EV phenotyping
- Flow cytometry
- Biomarker
- Glioblastoma
- Multiple sclerosis
- Alzheimer's disease
- Artikelnummer
- ARTN 276
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Titel
- Assessment of technical and clinical utility of a bead-based flow cytometry platform for multiparametric phenotyping of CNS-derived extracellular vesicles
- Sub types
- Article
- Ausgabe der Zeitschrift
- 21
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Extracellular vesicles (EVs) originating from the central nervous system (CNS) can enter the blood stream and carry molecules characteristic of disease states. Therefore, circulating CNS-derived EVs have the potential to serve as liquid-biopsy markers for early diagnosis and follow-up of neurodegenerative diseases and brain tumors. Monitoring and profiling of CNS-derived EVs using multiparametric analysis would be a major advance for biomarker as well as basic research. Here, we explored the performance of a multiplex bead-based flow-cytometry assay (EV Neuro) for semi-quantitative detection of CNS-derived EVs in body fluids. </jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>EVs were separated from culture of glioblastoma cell lines (LN18, LN229, NCH82) and primary human astrocytes and measured at different input amounts in the MACSPlex EV Kit Neuro, human. In addition, EVs were separated from blood samples of small cohorts of glioblastoma (GB), multiple sclerosis (MS) and Alzheimer’s disease patients as well as healthy controls (HC) and subjected to the EV Neuro assay. To determine statistically significant differences between relative marker signal intensities, an unpaired samples t-test or Wilcoxon rank sum test were computed. Data were subjected to tSNE, heatmap clustering, and correlation analysis to further explore the relationships between disease state and EV Neuro data. </jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Glioblastoma cell lines and primary human astrocytes showed distinct EV profiles. Signal intensities were increasing with higher EV input. Data normalization improved identification of markers that deviate from a common profile. Overall, patient blood-derived EV marker profiles were constant, but individual EV populations were significantly increased in disease compared to healthy controls, e.g. CD36<jats:sup>+</jats:sup>EVs in glioblastoma and GALC<jats:sup>+</jats:sup>EVs in multiple sclerosis. tSNE and heatmap clustering analysis separated GB patients from HC, but not MS patients from HC. Correlation analysis revealed a potential association of CD107a<jats:sup>+</jats:sup>EVs with neurofilament levels in blood of MS patients and HC. </jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The semi-quantitative EV Neuro assay demonstrated its utility for EV profiling in complex samples. However, reliable statistical results in biomarker studies require large sample cohorts and high effect sizes. Nonetheless, this exploratory trial confirmed the feasibility of discovering EV-associated biomarkers and monitoring circulating EV profiles in CNS diseases using the EV Neuro assay.</jats:p> </jats:sec>
- Autoren
- Alexandra Brahmer
- Carsten Geiß
- Andriani Lygeraki
- Elmo Neuberger
- Theophilos Tzaridis
- Tinh Thi Nguyen
- Felix Luessi
- Anne Régnier-Vigouroux
- Gunther Hartmann
- Perikles Simon
- Kristina Endres
- Stefan Bittner
- Katrin S Reiners
- Eva-Maria Krämer-Albers
- DOI
- 10.1186/s12964-023-01308-9
- eISSN
- 1478-811X
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Cell Communication and Signaling
- Sprache
- en
- Artikelnummer
- 276
- Online publication date
- 2023
- Status
- Published online
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1186/s12964-023-01308-9
- Datum der Datenerfassung
- 2023
- Titel
- Assessment of technical and clinical utility of a bead-based flow cytometry platform for multiparametric phenotyping of CNS-derived extracellular vesicles
- Ausgabe der Zeitschrift
- 21
Datenquelle: Crossref
- Abstract
- <h4>Background</h4>Extracellular vesicles (EVs) originating from the central nervous system (CNS) can enter the blood stream and carry molecules characteristic of disease states. Therefore, circulating CNS-derived EVs have the potential to serve as liquid-biopsy markers for early diagnosis and follow-up of neurodegenerative diseases and brain tumors. Monitoring and profiling of CNS-derived EVs using multiparametric analysis would be a major advance for biomarker as well as basic research. Here, we explored the performance of a multiplex bead-based flow-cytometry assay (EV Neuro) for semi-quantitative detection of CNS-derived EVs in body fluids.<h4>Methods</h4>EVs were separated from culture of glioblastoma cell lines (LN18, LN229, NCH82) and primary human astrocytes and measured at different input amounts in the MACSPlex EV Kit Neuro, human. In addition, EVs were separated from blood samples of small cohorts of glioblastoma (GB), multiple sclerosis (MS) and Alzheimer's disease patients as well as healthy controls (HC) and subjected to the EV Neuro assay. To determine statistically significant differences between relative marker signal intensities, an unpaired samples t-test or Wilcoxon rank sum test were computed. Data were subjected to tSNE, heatmap clustering, and correlation analysis to further explore the relationships between disease state and EV Neuro data.<h4>Results</h4>Glioblastoma cell lines and primary human astrocytes showed distinct EV profiles. Signal intensities were increasing with higher EV input. Data normalization improved identification of markers that deviate from a common profile. Overall, patient blood-derived EV marker profiles were constant, but individual EV populations were significantly increased in disease compared to healthy controls, e.g. CD36<sup>+</sup>EVs in glioblastoma and GALC<sup>+</sup>EVs in multiple sclerosis. tSNE and heatmap clustering analysis separated GB patients from HC, but not MS patients from HC. Correlation analysis revealed a potential association of CD107a<sup>+</sup>EVs with neurofilament levels in blood of MS patients and HC.<h4>Conclusions</h4>The semi-quantitative EV Neuro assay demonstrated its utility for EV profiling in complex samples. However, reliable statistical results in biomarker studies require large sample cohorts and high effect sizes. Nonetheless, this exploratory trial confirmed the feasibility of discovering EV-associated biomarkers and monitoring circulating EV profiles in CNS diseases using the EV Neuro assay. Video Abstract.
- Addresses
- Cellular Neurobiology, Institute of Developmental Biology and Neurobiology, Johannes Gutenberg University of Mainz, Mainz, Germany. albrahme@uni-mainz.de.
- Autoren
- Alexandra Brahmer
- Carsten Geiß
- Andriani Lygeraki
- Elmo Neuberger
- Theophilos Tzaridis
- Tinh Thi Nguyen
- Felix Luessi
- Anne Régnier-Vigouroux
- Gunther Hartmann
- Perikles Simon
- Kristina Endres
- Stefan Bittner
- Katrin S Reiners
- Eva-Maria Krämer-Albers
- DOI
- 10.1186/s12964-023-01308-9
- eISSN
- 1478-811X
- Externe Identifier
- PubMed Identifier: 37803478
- PubMed Central ID: PMC10559539
- Funding acknowledgements
- SHARP initiative:
- Deutsche Forschungsgemeinschaft: CRC-TR-128
- Mainz Research Center for Mental Health:
- Deutsche Forschungsgemeinschaft: KR 3668/1-2
- Hermann und Lilly Schilling-Stiftung für Medizinische Forschung:
- Johannes Gutenberg-Universität Mainz:
- Open access
- true
- ISSN
- 1478-811X
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Cell communication and signaling : CCS
- Schlüsselwörter
- Central Nervous System
- Humans
- Glioblastoma
- Multiple Sclerosis
- Flow Cytometry
- Biomarkers
- Extracellular Vesicles
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2023
- Open access status
- Open Access
- Paginierung
- 276
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2023
- Titel
- Assessment of technical and clinical utility of a bead-based flow cytometry platform for multiparametric phenotyping of CNS-derived extracellular vesicles.
- Sub types
- Video-Audio Media
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 21
Files
https://biosignaling.biomedcentral.com/counter/pdf/10.1186/s12964-023-01308-9 https://europepmc.org/articles/PMC10559539?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- BACKGROUND: Extracellular vesicles (EVs) originating from the central nervous system (CNS) can enter the blood stream and carry molecules characteristic of disease states. Therefore, circulating CNS-derived EVs have the potential to serve as liquid-biopsy markers for early diagnosis and follow-up of neurodegenerative diseases and brain tumors. Monitoring and profiling of CNS-derived EVs using multiparametric analysis would be a major advance for biomarker as well as basic research. Here, we explored the performance of a multiplex bead-based flow-cytometry assay (EV Neuro) for semi-quantitative detection of CNS-derived EVs in body fluids. METHODS: EVs were separated from culture of glioblastoma cell lines (LN18, LN229, NCH82) and primary human astrocytes and measured at different input amounts in the MACSPlex EV Kit Neuro, human. In addition, EVs were separated from blood samples of small cohorts of glioblastoma (GB), multiple sclerosis (MS) and Alzheimer's disease patients as well as healthy controls (HC) and subjected to the EV Neuro assay. To determine statistically significant differences between relative marker signal intensities, an unpaired samples t-test or Wilcoxon rank sum test were computed. Data were subjected to tSNE, heatmap clustering, and correlation analysis to further explore the relationships between disease state and EV Neuro data. RESULTS: Glioblastoma cell lines and primary human astrocytes showed distinct EV profiles. Signal intensities were increasing with higher EV input. Data normalization improved identification of markers that deviate from a common profile. Overall, patient blood-derived EV marker profiles were constant, but individual EV populations were significantly increased in disease compared to healthy controls, e.g. CD36+EVs in glioblastoma and GALC+EVs in multiple sclerosis. tSNE and heatmap clustering analysis separated GB patients from HC, but not MS patients from HC. Correlation analysis revealed a potential association of CD107a+EVs with neurofilament levels in blood of MS patients and HC. CONCLUSIONS: The semi-quantitative EV Neuro assay demonstrated its utility for EV profiling in complex samples. However, reliable statistical results in biomarker studies require large sample cohorts and high effect sizes. Nonetheless, this exploratory trial confirmed the feasibility of discovering EV-associated biomarkers and monitoring circulating EV profiles in CNS diseases using the EV Neuro assay. Video Abstract.
- Date of acceptance
- 2023
- Autoren
- Alexandra Brahmer
- Carsten Geiß
- Andriani Lygeraki
- Elmo Neuberger
- Theophilos Tzaridis
- Tinh Thi Nguyen
- Felix Luessi
- Anne Régnier-Vigouroux
- Gunther Hartmann
- Perikles Simon
- Kristina Endres
- Stefan Bittner
- Katrin S Reiners
- Eva-Maria Krämer-Albers
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/37803478
- DOI
- 10.1186/s12964-023-01308-9
- eISSN
- 1478-811X
- Externe Identifier
- PubMed Central ID: PMC10559539
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Cell Commun Signal
- Schlüsselwörter
- Alzheimer’s disease
- Biomarker
- CNS diseases
- EV phenotyping
- Extracellular vesicles
- Flow cytometry
- Glioblastoma
- Multiple sclerosis
- Humans
- Glioblastoma
- Flow Cytometry
- Central Nervous System
- Extracellular Vesicles
- Biomarkers
- Multiple Sclerosis
- Sprache
- eng
- Country
- England
- Paginierung
- 276
- PII
- 10.1186/s12964-023-01308-9
- Datum der Veröffentlichung
- 2023
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2023
- Titel
- Assessment of technical and clinical utility of a bead-based flow cytometry platform for multiparametric phenotyping of CNS-derived extracellular vesicles.
- Sub types
- Video-Audio Media
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 21
Datenquelle: PubMed
- Author's licence
- CC-BY
- Autoren
- Alexandra Brahmer
- Carsten Geiß
- Andriani Lygeraki
- Elmo Neuberger
- Theophilos Tzaridis
- Tinh Thi Nguyen
- Felix Luessi
- Anne Régnier-Vigouroux
- Gunther Hartmann
- Perikles Simon
- Kristina Endres
- Stefan Bittner
- Katrin S Reiners
- Eva-Maria Krämer-Albers
- Hosting institution
- Universitätsbibliothek Mainz
- Sammlungen
- DFG-491381577-G
- Resource version
- Published version
- DOI
- 10.1186/s12964-023-01308-9
- File(s) embargoed
- false
- Open access
- true
- ISSN
- 1478-811X
- Zeitschrift
- Cell communication and signaling
- Schlüsselwörter
- 570 Biowissenschaften
- 570 Life sciences
- Sprache
- eng
- Open access status
- Open Access
- Paginierung
- 276
- Datum der Veröffentlichung
- 2023
- Public URL
- https://openscience.ub.uni-mainz.de/handle/20.500.12030/9806
- Herausgeber
- Biomed Central
- Datum der Datenerfassung
- 2023
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2023
- Zugang
- Public
- Titel
- Assessment of technical and clinical utility of a bead-based flow cytometry platform for multiparametric phenotyping of CNS-derived extracellular vesicles
- Ausgabe der Zeitschrift
- 21
Files
assessment_of_technical_and_c-20231211122457467.pdf
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