A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation

  • Martin Wolf
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Rodolphe W. Poupardin
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Patricia Ebner‐Peking
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • André Cronemberger Andrade
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Constantin Blöchl
    Department of Biosciences Paris Lodron University Salzburg Salzburg Austria
  • Astrid Obermayer
    Department of Biosciences Paris Lodron University Salzburg Salzburg Austria
  • Fausto Gueths Gomes
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Balazs Vari
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Nicole Maeding
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Essi Eminger
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Heide‐Marie Binder
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Anna M. Raninger
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Sarah Hochmann
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Gabriele Brachtl
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
  • Andreas Spittler
    Core Facility Flow Cytometry and Department of Surgery Research Laboratories Medical University of Vienna Vienna Austria
  • Thomas Heuser
    Vienna Biocentre Core Facilities Vienna Austria
  • Racheli Ofir
    Pluristem Ltd. Haifa Israel
  • Christian G. Huber
    Department of Biosciences Paris Lodron University Salzburg Salzburg Austria
  • Zami Aberman
    Pluristem Ltd. Haifa Israel
  • Katharina Schallmoser
    Department of Transfusion Medicine and SCI‐TReCS PMU Salzburg Austria
  • Hans‐Dieter Volk
    Berlin Institute of Health at Charité – Universitätsmedizin BIH Centre for Regenerative Therapies (BCRT) Berlin Germany
  • Dirk Strunk
    Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria

書誌事項

公開日
2022-04
権利情報
  • http://creativecommons.org/licenses/by/4.0/
DOI
  • 10.1002/jev2.12207
公開者
Wiley

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説明

<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

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