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Post-production modifications of murine mesenchymal stem cell (mMSC) derived extracellular vesicles (EVs) and impact on their cellular interaction.

Authors
  • Le Saux, Sarah1
  • Aarrass, Hanna1
  • Lai-Kee-Him, Joséphine2
  • Bron, Patrick2
  • Armengaud, Jean3
  • Miotello, Guylaine3
  • Bertrand-Michel, Justine4
  • Dubois, Emeric5
  • George, Simon5
  • Faklaris, Orestis6
  • Devoisselle, Jean-Marie1
  • Legrand, Philippe1
  • Chopineau, Joël7
  • Morille, Marie8
  • 1 ICGM, Univ Montpellier, ENSCM, CNRS, Montpellier, France. , (France)
  • 2 CBS, Univ Montpellier, INSERM, CNRS, Montpellier, France. , (France)
  • 3 Laboratory «Innovative technologies for Detection and Diagnostics», CEA-Marcoule, DRF/JOLIOT/DMTS/SPI/Li2D, Bagnols-sur-Cèze, France. , (France)
  • 4 MetaToul-LIPIDOMIQUE, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) Inserm/Université Paul Sabatier UMR1048, Toulouse, France. , (France)
  • 5 MGX-Montpellier GenomiX, IGF, CNRS, INSERM, Univ Montpellier, Montpellier, France. , (France)
  • 6 Montpellier Ressources Imagerie, Biocampus, CNRS, INSERM, Univ Montpellier, Montpellier, France. , (France)
  • 7 ICGM, Univ Montpellier, ENSCM, CNRS, Montpellier, France; Université de Nîmes, Nîmes, France. , (France)
  • 8 ICGM, Univ Montpellier, ENSCM, CNRS, Montpellier, France. Electronic address: [email protected] , (France)
Type
Published Article
Journal
Biomaterials
Publication Date
Dec 07, 2019
Volume
231
Pages
119675–119675
Identifiers
DOI: 10.1016/j.biomaterials.2019.119675
PMID: 31838346
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

In regards to their key role in intercellular communication, extracellular vesicles (EVs) have a strong potential as bio-inspired drug delivery systems (DDS). With the aim of circumventing some of their well-known issues (production yield, drug loading yield, pharmacokinetics), we specifically focused on switching the biological vision of these entities to a more physico-chemical one, and to consider and fine-tune EVs as synthetic vectors. To allow a rational use, we first performed a full physico-chemical (size, concentration, surface charge, cryoTEM), biochemical (western blot, proteomics, lipidomics, transcriptomics) and biological (cell internalisation) characterisation of murine mesenchymal stem cell (mMSC)-derived EVs. A stability study based on evaluating the colloidal behaviour of obtained vesicles was performed in order to identify optimal storage conditions. We evidenced the interest of using EVs instead of liposomes, in regards to target cell internalisation efficiency. EVs were shown to be internalised through a caveolae and cholesterol-dependent pathway, following a different endocytic route than liposomes. Then, we characterised the effect of physical methods scarcely investigated with EVs (extrusion through 50 nm membranes, freeze-drying, sonication) on EV size, concentration, structure and cell internalisation properties. Our extensive characterisation of the effect of these physical processes highlights their promise as loading methods to make EVs efficient delivery vehicles. Copyright © 2019. Published by Elsevier Ltd.

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