A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation
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- Martin Wolf
- Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
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- Rodolphe W. Poupardin
- Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
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- Patricia Ebner‐Peking
- Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
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- André Cronemberger Andrade
- Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
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- Constantin Blöchl
- Department of Biosciences Paris Lodron University Salzburg Salzburg Austria
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- Astrid Obermayer
- Department of Biosciences Paris Lodron University Salzburg Salzburg Austria
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- Fausto Gueths Gomes
- Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
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- Balazs Vari
- Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
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- Nicole Maeding
- Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
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- Essi Eminger
- Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
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- Heide‐Marie Binder
- Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
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- Anna M. Raninger
- Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
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- Sarah Hochmann
- Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
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- Gabriele Brachtl
- Cell Therapy Institute Spinal Cord Injury and Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University (PMU) Salzburg Austria
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- Andreas Spittler
- Core Facility Flow Cytometry and Department of Surgery Research Laboratories Medical University of Vienna Vienna Austria
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- Thomas Heuser
- Vienna Biocentre Core Facilities Vienna Austria
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- Racheli Ofir
- Pluristem Ltd. Haifa Israel
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- Christian G. Huber
- Department of Biosciences Paris Lodron University Salzburg Salzburg Austria
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- Zami Aberman
- Pluristem Ltd. Haifa Israel
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- Katharina Schallmoser
- Department of Transfusion Medicine and SCI‐TReCS PMU Salzburg Austria
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- Hans‐Dieter Volk
- Berlin Institute of Health at Charité – Universitätsmedizin BIH Centre for Regenerative Therapies (BCRT) Berlin Germany
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- 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
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- http://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.1002/jev2.12207
- 公開者
- Wiley
この論文をさがす
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>
収録刊行物
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- Journal of Extracellular Vesicles
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Journal of Extracellular Vesicles 11 (4), 2022-04
Wiley
