Heparan sulfate proteoglycan-mediated dynamin-dependent transport of neural stem cell exosomes in an in vitro blood-brain barrier model

Bhagyashree S Joshi, Inge S Zuhorn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
51 Downloads (Pure)

Abstract

Drug delivery to the brain is greatly hampered by the presence of the blood-brain barrier (BBB) which tightly regulates the passage of molecules from blood to brain and vice versa. Nanocarriers, in which drugs can be encapsulated, can move across the blood-brain barrier (BBB) via the process of transcytosis, thus showing promise to improve drug delivery to the brain. Here, we demonstrate the use of natural nanovesicles, that is, exosomes, derived from C17.2 neural stem cells (NSCs) to efficiently carry a protein cargo across an in vitro BBB model consisting of human brain microvascular endothelial cells. We show that the exosomes are primarily taken up in brain endothelial cells via endocytosis, while heparan sulfate proteoglycans (HSPGs) act as receptors. Taken together, our data support the view that NSC exosomes may act as biological nanocarriers for efficient passage across the BBB. Nanomedicines that target HSPGs may improve their binding to brain endothelial cells and, possibly, show subsequent transcytosis across the BBB.

Original languageEnglish
Pages (from-to)706-719
Number of pages14
JournalEuropean Journal of Neuroscience
Volume53
Issue number3
Early online date16-Sep-2020
DOIs
Publication statusPublished - Feb-2021

Keywords

  • blood-brain barrier
  • cargo
  • endothelial cell
  • exosomes
  • extracellular vesicles
  • heparan sulfate proteoglycans
  • nanocarriers
  • transcytosis
  • DELIVERY VEHICLES
  • ENDOTHELIAL-CELLS
  • SYSTEMIC DELIVERY
  • LEUKEMIA-VIRUS
  • PROTEIN
  • RECEPTORS
  • MECHANISM
  • VESICLES
  • GROWTH
  • INTERNALIZATION

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