A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation.
Wolf Martin, Poupardin Rodolphe W, Ebner-Peking Patricia, Andrade André Cronemberger, Blöchl Constantin, Obermayer Astrid, Gomes Fausto Gueths, Vari Balazs, Maeding Nicole, Eminger Essi, Binder Heide-Marie, Raninger Anna M, Hochmann Sarah, Brachtl Gabriele, Spittler Andreas, Heuser Thomas, Ofir Racheli, Huber Christian G, Aberman Zami, Schallmoser Katharina, Volk Hans-Dieter, Strunk Dirk
Journal of extracellular vesicles · 2022 · PMID 35398993 · 인용 276
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.