Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles

J Nanobiotechnology. 2020 Dec 7;18(1):178. doi: 10.1186/s12951-020-00739-7.

Abstract

Background: Mesenchymal stem cells (MSCs) are pluripotent stromal cells that release extracellular vesicles (EVs). EVs contain various growth factors and antioxidants that can positively affect the surrounding cells. Nanoscale MSC-derived EVs, such as exosomes, have been developed as bio-stable nano-type materials. However, some issues, such as low yield and difficulty in quantification, limit their use. We hypothesized that enhancing exosome production using nanoparticles would stimulate the release of intracellular molecules.

Results: The aim of this study was to elucidate the molecular mechanisms of exosome generation by comparing the internalization of surface-modified, positively charged nanoparticles and exosome generation from MSCs. We determined that Rab7, a late endosome and auto-phagosome marker, was increased upon exosome expression and was associated with autophagosome formation.

Conclusions: It was concluded that the nanoparticles we developed were transported to the lysosome by clathrin-mediated endocytosis. additionally, entered nanoparticles stimulated that autophagy related factors to release exosome from the MSC. MSC-derived exosomes using nanoparticles may increase exosome yield and enable the discovery of nanoparticle-induced genetic factors.

Keywords: Autophagy; Mesenchymal stem cell-derived exosome; PLGA-PEI NPs; Positively charged nanoparticle; Rab7.

MeSH terms

  • Animals
  • Autophagy / genetics
  • Cells, Cultured
  • Exosomes* / chemistry
  • Exosomes* / metabolism
  • Magnetite Nanoparticles / chemistry*
  • Mesenchymal Stem Cells* / chemistry
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • MicroRNAs / metabolism
  • Polyethyleneimine / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Surface Properties
  • rab GTP-Binding Proteins / metabolism
  • rab7 GTP-Binding Proteins

Substances

  • Magnetite Nanoparticles
  • MicroRNAs
  • rab7 GTP-Binding Proteins
  • rab7 GTP-binding proteins, mouse
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyethyleneimine
  • rab GTP-Binding Proteins