Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses
Abstract Cardiac progenitor cell (CPC)‐derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding the distinct mechanisms underlying their regenerative abilities. Here, a...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
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| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.12396 |
| _version_ | 1797346211455303680 |
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| author | Simonides Immanuel van deWakker Julia Bauzá‐Martinez Carla Ríos Arceo Herak Manjikian Christian Jamie Bernard Snijders Blok Marieke Theodora Roefs Eduard Willms Renee Goverdina Catharina Maas Matti Feije Pronker Olivier Gerrit deJong Wei Wu André Görgens Samir El Andaloussi Joost Petrus Gerardus Sluijter Pieter Vader |
| author_facet | Simonides Immanuel van deWakker Julia Bauzá‐Martinez Carla Ríos Arceo Herak Manjikian Christian Jamie Bernard Snijders Blok Marieke Theodora Roefs Eduard Willms Renee Goverdina Catharina Maas Matti Feije Pronker Olivier Gerrit deJong Wei Wu André Görgens Samir El Andaloussi Joost Petrus Gerardus Sluijter Pieter Vader |
| author_sort | Simonides Immanuel van deWakker |
| collection | DOAJ |
| description | Abstract Cardiac progenitor cell (CPC)‐derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding the distinct mechanisms underlying their regenerative abilities. Here, a dual‐step multimodal flowthrough and size‐exclusion chromatography method was applied to isolate and separate CPC‐derived sEV subpopulations to study the functional differences related to cardiac repair responses. Three distinct sEV subpopulations were identified with unique protein profiles. Functional cell assays for cardiac repair‐related processes demonstrated that the middle‐sized and smallest‐sized sEV subpopulations exhibited the highest pro‐angiogenic and anti‐fibrotic activities. Proteasome activity was uniquely seen in the smallest‐sized subpopulation. The largest‐sized subpopulation showed no effect in any of the functional assays. This research uncovers the existence of sEV subpopulations, each characterized by a distinct composition and biological function. Enhancing our understanding of sEV heterogeneity will provide valuable insights into sEV mechanisms of action, ultimately accelerating the translation of sEV therapeutics. |
| first_indexed | 2024-03-08T11:29:45Z |
| format | Article |
| id | doaj.art-216f54e574094a04966cba7e541ce4bb |
| institution | Directory Open Access Journal |
| issn | 2001-3078 |
| language | English |
| last_indexed | 2024-03-08T11:29:45Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj.art-216f54e574094a04966cba7e541ce4bb2024-01-26T03:51:18ZengWileyJournal of Extracellular Vesicles2001-30782024-01-01131n/an/a10.1002/jev2.12396Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responsesSimonides Immanuel van deWakker0Julia Bauzá‐Martinez1Carla Ríos Arceo2Herak Manjikian3Christian Jamie Bernard Snijders Blok4Marieke Theodora Roefs5Eduard Willms6Renee Goverdina Catharina Maas7Matti Feije Pronker8Olivier Gerrit deJong9Wei Wu10André Görgens11Samir El Andaloussi12Joost Petrus Gerardus Sluijter13Pieter Vader14Department of Experimental Cardiology, Regenerative Medicine Center Utrecht, Circulatory health Research Center University Utrecht, University Medical Center Utrecht Utrecht The NetherlandsBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The NetherlandsDepartment of Experimental Cardiology, Regenerative Medicine Center Utrecht, Circulatory health Research Center University Utrecht, University Medical Center Utrecht Utrecht The NetherlandsDepartment of Experimental Cardiology, Regenerative Medicine Center Utrecht, Circulatory health Research Center University Utrecht, University Medical Center Utrecht Utrecht The NetherlandsDepartment of Experimental Cardiology, Regenerative Medicine Center Utrecht, Circulatory health Research Center University Utrecht, University Medical Center Utrecht Utrecht The NetherlandsDepartment of Experimental Cardiology, Regenerative Medicine Center Utrecht, Circulatory health Research Center University Utrecht, University Medical Center Utrecht Utrecht The NetherlandsDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science La Trobe University Melbourne AustraliaDepartment of Experimental Cardiology, Regenerative Medicine Center Utrecht, Circulatory health Research Center University Utrecht, University Medical Center Utrecht Utrecht The NetherlandsBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The NetherlandsDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS) Utrecht University Utrecht The NetherlandsBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The NetherlandsDepartment of Laboratory Medicine Karolinska Institute Stockholm, Huddinge SwedenDepartment of Laboratory Medicine Karolinska Institute Stockholm, Huddinge SwedenDepartment of Experimental Cardiology, Regenerative Medicine Center Utrecht, Circulatory health Research Center University Utrecht, University Medical Center Utrecht Utrecht The NetherlandsDepartment of Experimental Cardiology, Regenerative Medicine Center Utrecht, Circulatory health Research Center University Utrecht, University Medical Center Utrecht Utrecht The NetherlandsAbstract Cardiac progenitor cell (CPC)‐derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding the distinct mechanisms underlying their regenerative abilities. Here, a dual‐step multimodal flowthrough and size‐exclusion chromatography method was applied to isolate and separate CPC‐derived sEV subpopulations to study the functional differences related to cardiac repair responses. Three distinct sEV subpopulations were identified with unique protein profiles. Functional cell assays for cardiac repair‐related processes demonstrated that the middle‐sized and smallest‐sized sEV subpopulations exhibited the highest pro‐angiogenic and anti‐fibrotic activities. Proteasome activity was uniquely seen in the smallest‐sized subpopulation. The largest‐sized subpopulation showed no effect in any of the functional assays. This research uncovers the existence of sEV subpopulations, each characterized by a distinct composition and biological function. Enhancing our understanding of sEV heterogeneity will provide valuable insights into sEV mechanisms of action, ultimately accelerating the translation of sEV therapeutics.https://doi.org/10.1002/jev2.12396extracellular vesicle functionextracellular vesiclesheterogeneityregenerative medicinesubpopulations |
| spellingShingle | Simonides Immanuel van deWakker Julia Bauzá‐Martinez Carla Ríos Arceo Herak Manjikian Christian Jamie Bernard Snijders Blok Marieke Theodora Roefs Eduard Willms Renee Goverdina Catharina Maas Matti Feije Pronker Olivier Gerrit deJong Wei Wu André Görgens Samir El Andaloussi Joost Petrus Gerardus Sluijter Pieter Vader Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses Journal of Extracellular Vesicles extracellular vesicle function extracellular vesicles heterogeneity regenerative medicine subpopulations |
| title | Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses |
| title_full | Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses |
| title_fullStr | Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses |
| title_full_unstemmed | Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses |
| title_short | Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses |
| title_sort | size matters functional differences of small extracellular vesicle subpopulations in cardiac repair responses |
| topic | extracellular vesicle function extracellular vesicles heterogeneity regenerative medicine subpopulations |
| url | https://doi.org/10.1002/jev2.12396 |
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