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

Simonides Immanuel van de WakkerJulia Bauzá-MartinezCarla Ríos ArceoHerak ManjikianChristian Jamie Bernard Snijders BlokMarieke Theodora RoefsEduard WillmsRenee Goverdina Catharina MaasMatti Feije PronkerOlivier Gerrit de JongWei WuAndre GörgensSamir El AndaloussiJoost Petrus Gerardus SluijterPieter Vader
Published in: Journal of extracellular vesicles (2024)
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.
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