Interfering with endolysosomal trafficking enhances release of bioactive exosomes

Francisco G Ortega, Marieke T Roefs, Diego de Miguel Perez, Sander A Kooijmans, Olivier G de Jong, Joost P Sluijter, Raymond M Schiffelers, Pieter Vader

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Exosomes are cell-derived extracellular vesicles of 30-150 nm in size and are involved in intercellular communication. Because of their bioactive cargo, consisting of proteins, RNA and lipids, and their natural ability to deliver these biomolecules to recipient cells, exosomes are increasingly being studied as novel drug delivery vehicles or as cell-free approaches to regenerative medicine. However, one of the major hurdles for clinical translation of therapeutic strategies based on exosomes is their low yield when produced under standard culture conditions. Exosomes are vesicles of endocytic origin and are released when multivesicular endosomes fuse with the plasma membrane. Here, we demonstrate that interfering with endolysosomal trafficking significantly increases exosome release. Furthermore, these exosomes retain their regenerative bioactivity as demonstrated by pro-survival and angiogenesis assays using both cardiomyocytes and endothelial cells. These results may be employed to increase exosome production for studying biological functions or to improve clinical translation of exosome-based therapeutics.

Original languageEnglish
Pages (from-to)102014
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume20
DOIs
Publication statusPublished - Aug 2019

Keywords

  • Ammonium Chloride/pharmacology
  • Biological Transport/drug effects
  • Biomarkers/metabolism
  • Cell Cycle Proteins/metabolism
  • Cell Line, Tumor
  • Chloroquine/pharmacology
  • Endosomes/drug effects
  • Endothelial Cells/drug effects
  • Exosomes/drug effects
  • Humans
  • Intracellular Signaling Peptides and Proteins/metabolism
  • Lysosomes/drug effects
  • MAP Kinase Signaling System/drug effects
  • Myocardium/cytology
  • Neovascularization, Physiologic/drug effects
  • Phosphorylation/drug effects
  • Proto-Oncogene Proteins c-akt/metabolism
  • Stem Cells/cytology

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