A functional corona around extracellular vesicles enhances angiogenesis during skin regeneration and signals in immune cells

Citations Over Time

Abstract

Nanoparticles can acquire a protein corona defining their biological identity. Corona functions were not yet considered for cell-derived extracellular vesicles (EVs). Here we demonstrate that nanosized 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 and subtractive tandem mass-tag 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 protected corona proteins from protease digestion. EVs significantly ameliorated human skin regeneration and angiogenesis in vivo, induced differential signaling 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 defined proangiogenic proteins served as a proof-of-concept. Understanding EV corona formation will improve rational EV-inspired nanotherapy design.

Related Papers

• → Progress, opportunity, and perspective on exosome isolation - efforts for efficient exosome-based theranostics(2020)969 cited
• → Physical exosome:exosome interactions(2018)150 cited
• → Current Strategies for Promoting the Large-scale Production ofExosomes(2023)55 cited
• → Unraveling the physiological functions of exosome secretion by tumors(2013)43 cited
• → Role of Exosomes in Tuberculosis: Looking towards a Future Road Map(2023)1 cited