A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation.
EV corona
EV function
angiogenesis
extracelular vesicle
placenta derived stromal cells
tangential flow filtration
Journal
Journal of extracellular vesicles
ISSN: 2001-3078
Titre abrégé: J Extracell Vesicles
Pays: United States
ID NLM: 101610479
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
08
02
2022
received:
01
10
2021
accepted:
02
03
2022
entrez:
10
4
2022
pubmed:
11
4
2022
medline:
13
4
2022
Statut:
ppublish
Résumé
Nanoparticles can acquire a plasma protein corona defining their biological identity. Corona functions were previously considered for cell-derived extracellular vesicles (EVs). Here we demonstrate that nano-sized EVs from therapy-grade human placental-expanded (PLX) stromal cells are surrounded by an imageable and functional protein corona when enriched with permissive technology. Scalable EV separation from cell-secreted soluble factors via tangential flow-filtration (TFF) and subtractive tandem mass-tag (TMT) proteomics revealed significant enrichment of predominantly immunomodulatory and proangiogenic proteins. Western blot, calcein-based flow cytometry, super-resolution and electron microscopy verified EV identity. PLX-EVs partly protected corona proteins from protease digestion. EVs significantly ameliorated human skin regeneration and angiogenesis in vivo, induced differential signalling in immune cells, and dose-dependently inhibited T cell proliferation in vitro. Corona removal by size-exclusion or ultracentrifugation abrogated angiogenesis. Re-establishing an artificial corona by cloaking EVs with fluorescent albumin as a model protein or defined proangiogenic factors was depicted by super-resolution microscopy, electron microscopy and zeta-potential shift, and served as a proof-of-concept. Understanding EV corona formation will improve rational EV-inspired nano-therapy design.
Identifiants
pubmed: 35398993
doi: 10.1002/jev2.12207
pmc: PMC8994701
doi:
Substances chimiques
Protein Corona
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12207Subventions
Organisme : Land Salzburg
ID : 20102-F2100572-FPREV-Quant
Organisme : Land Salzburg
ID : IWB/EFRE P1812596
Organisme : Land Salzburg
ID : WISS 2025 20102-F1900731-KZP EV-TT
Organisme : Land Salzburg
ID : F2000237-FIPSTEBS
Organisme : Austrian Science Fund
ID : W1213
Organisme : European Commission
ID : 731377
Organisme : European Commission
ID : 733006
Organisme : F 2000237-FIP "STEBS"
Informations de copyright
© 2022 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.
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