Human Adipose Tissue-Derived Mesenchymal Stem Cells Secrete Functional Neprilysin-Bound Exosomes

Sci Rep. 2013;3:1197. doi: 10.1038/srep01197. Epub 2013 Feb 1.

Abstract

Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid peptide (Aβ) in the brain because of an imbalance between Aβ production and clearance. Neprilysin (NEP) is the most important Aβ-degrading enzyme in the brain. Thus, researchers have explored virus-mediated NEP gene delivery. However, such strategies may entail unexpected risks, and thus exploration of a new possibility for NEP delivery is also required. Here, we show that human adipose tissue-derived mesenchymal stem cells (ADSCs) secrete exosomes carrying enzymatically active NEP. The NEP-specific activity level of 1 μg protein from ADSC-derived exosomes was equivalent to that of ~ 0.3 ng of recombinant human NEP. Of note, ADSC-derived exosomes were transferred into N2a cells, and were suggested to decrease both secreted and intracellular Aβ levels in the N2a cells. Importantly, these characteristics were more pronounced in ADSCs than bone marrow-derived mesenchymal stem cells, suggesting the therapeutic relevance of ADSC-derived exosomes for AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Cells, Cultured
  • Exosomes / metabolism*
  • Fluorescent Dyes / chemistry
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Neprilysin / genetics
  • Neprilysin / metabolism*
  • Peptide Fragments / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics

Substances

  • Amyloid beta-Peptides
  • Fluorescent Dyes
  • Peptide Fragments
  • Recombinant Proteins
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • Neprilysin