Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses

Simonides Immanuel van de Wakker; 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 de Jong; Wei Wu; André Görgens; Samir El Andaloussi; Joost Petrus Gerardus Sluijter; Pieter Vader

doi:10.1002/jev2.12396

Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses

Simonides Immanuel van de Wakker
, 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 de Jong
, Wei Wu
, André Görgens
, Samir El Andaloussi
, Joost Petrus Gerardus Sluijter
, Pieter Vader^*

^*Corresponding author for this work

Utrecht University, University Medical Center Utrecht
Utrecht University, University Medical Center Utrecht
Utrecht University, University Medical Center Utrecht
Utrecht University, University Medical Center Utrecht
La Trobe University
Karolinska Institutet

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	12396
Number of pages	21
Journal	Journal of Extracellular Vesicles
Volume	13
Issue number	1
DOIs	https://doi.org/10.1002/jev2.12396
Publication status	Published - 5 Jan 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.

Funding

This work is financially supported by a Van Herk Foundation grant, ESC First Contact Initiative Grant, MDR Young Talent Incentives Program, NLSEV-MOVE and Erasmus+ grant to SvdW, an NWO Veni grant to MFP (VI.Veni.202.27), an ERC Consolidator Grant EVICARE (#725229) of the European Research Council (ERC) to JS, and a PPS grant (No. 2018B014) to JS and PV.

Funders	Funder number
MDR Young Talent Incentives Program
NLSEV-MOVE
Van Herk Foundation
European Research Council	2018B014
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	725229, VI.Veni.202.27
European Society of Contraception and Reproductive Health
Erasmus+

Keywords

extracellular vesicle function
extracellular vesicles
heterogeneity
regenerative medicine
subpopulations

Access to Document

10.1002/jev2.12396Licence: CC BY

J of Extracellular Vesicle - 2024 - Wakker - Size matters Functional differences of small extracellular vesicle (1)Final published version, 2.31 MBLicence: CC BY

Cite this

van de Wakker, S. I., Bauzá-Martinez, J., Ríos Arceo, C., Manjikian, H., Snijders Blok, C. J. B., Roefs, M. T., Willms, E., Maas, R. G. C., Pronker, M. F., de Jong, O. G., Wu, W., Görgens, A., El Andaloussi, S., Sluijter, J. P. G., & Vader, P. (2024). Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses. Journal of Extracellular Vesicles, 13(1), Article 12396. https://doi.org/10.1002/jev2.12396

@article{56d366a855714bbb8893cc20f36debd9,

title = "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 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.",

keywords = "extracellular vesicle function, extracellular vesicles, heterogeneity, regenerative medicine, subpopulations",

author = "\{van de Wakker\}, \{Simonides Immanuel\} and Julia Bauz{\'a}-Martinez and \{R{\'i}os Arceo\}, Carla and Herak Manjikian and \{Snijders Blok\}, \{Christian Jamie Bernard\} and Roefs, \{Marieke Theodora\} and Eduard Willms and Maas, \{Renee Goverdina Catharina\} and Pronker, \{Matti Feije\} and \{de Jong\}, \{Olivier Gerrit\} and Wei Wu and Andr{\'e} G{\"o}rgens and \{El Andaloussi\}, Samir and Sluijter, \{Joost Petrus Gerardus\} and Pieter Vader",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.",

year = "2024",

month = jan,

day = "5",

doi = "10.1002/jev2.12396",

language = "English",

volume = "13",

journal = "Journal of Extracellular Vesicles",

issn = "2001-3078",

publisher = "Wiley",

number = "1",

}

van de Wakker, SI, Bauzá-Martinez, J, Ríos Arceo, C, Manjikian, H, Snijders Blok, CJB, Roefs, MT, Willms, E, Maas, RGC, Pronker, MF, de Jong, OG, Wu, W, Görgens, A, El Andaloussi, S, Sluijter, JPG & Vader, P 2024, 'Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses', Journal of Extracellular Vesicles, vol. 13, no. 1, 12396. https://doi.org/10.1002/jev2.12396

TY - JOUR

T1 - Size matters

T2 - Functional differences of small extracellular vesicle subpopulations in cardiac repair responses

AU - van de Wakker, Simonides Immanuel

AU - Bauzá-Martinez, Julia

AU - Ríos Arceo, Carla

AU - Manjikian, Herak

AU - Snijders Blok, Christian Jamie Bernard

AU - Roefs, Marieke Theodora

AU - Willms, Eduard

AU - Maas, Renee Goverdina Catharina

AU - Pronker, Matti Feije

AU - de Jong, Olivier Gerrit

AU - Wu, Wei

AU - Görgens, André

AU - El Andaloussi, Samir

AU - Sluijter, Joost Petrus Gerardus

AU - Vader, Pieter

PY - 2024/1/5

Y1 - 2024/1/5

N2 - 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.

AB - 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.

KW - extracellular vesicle function

KW - extracellular vesicles

KW - heterogeneity

KW - regenerative medicine

KW - subpopulations

UR - https://www.scopus.com/pages/publications/85181629382

U2 - 10.1002/jev2.12396

DO - 10.1002/jev2.12396

M3 - Article

C2 - 38179654

SN - 2001-3078

VL - 13

JO - Journal of Extracellular Vesicles

JF - Journal of Extracellular Vesicles

IS - 1

M1 - 12396

ER -

Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this