title: Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes.
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.
authors: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors: Takeshi
authors: T
authors: Katsuda
authors: Reiko
authors: R
authors: Tsuchiya
authors: Nobuyoshi
authors: N
authors: Kosaka
authors: Yusuke
authors: Y
authors: Yoshioka
authors: Kentaro
authors: K
authors: Takagaki
authors: Katsuyuki
authors: K
authors: Oki
authors: Fumitaka
authors: F
authors: Takeshita
authors: Yasuyuki
authors: Y
authors: Sakai
authors: Masahiko
authors: M
authors: Kuroda
authors: Takahiro
authors: T
authors: Ochiya
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002478:Cells, Cultured; D055354:Exosomes / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D011994:Recombinant Proteins; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D015260:Neprilysin
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