Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes

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 deli...

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Published in	Scientific reports Vol. 3; no. 1; p. 1197
Main Authors	Katsuda, Takeshi, Tsuchiya, Reiko, Kosaka, Nobuyoshi, Yoshioka, Yusuke, Takagaki, Kentaro, Oki, Katsuyuki, Takeshita, Fumitaka, Sakai, Yasuyuki, Kuroda, Masahiko, Ochiya, Takahiro
Format	Journal Article
Language	English
Published	London Nature Publishing Group UK 01.02.2013 Nature Publishing Group
Subjects	631/378/340 631/45/607/468 631/532/2074 631/61/2297 Adipose tissue Adipose Tissue - cytology Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer's disease Amyloid beta-Peptides - metabolism Bone marrow Cells, Cultured Exosomes Exosomes - metabolism Fluorescent Dyes - chemistry Gene transfer Humanities and Social Sciences Humans Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - metabolism Mesenchymal Stromal Cells - secretion Mesenchyme multidisciplinary Nep gene Neprilysin Neprilysin - genetics Neprilysin - metabolism Neprilysin - secretion Neurodegenerative diseases Peptide Fragments - metabolism Recombinant Proteins - biosynthesis Recombinant Proteins - genetics Science Skin & tissue grafts Stem cells β-Amyloid
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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.
AbstractList	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. 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.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.
ArticleNumber	1197
Author	Kuroda, Masahiko Tsuchiya, Reiko Takagaki, Kentaro Sakai, Yasuyuki Takeshita, Fumitaka Ochiya, Takahiro Katsuda, Takeshi Kosaka, Nobuyoshi Yoshioka, Yusuke Oki, Katsuyuki
Author_xml	– sequence: 1 givenname: Takeshi surname: Katsuda fullname: Katsuda, Takeshi organization: From the Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Institute of Industrial Science (IIS), The University of Tokyo – sequence: 2 givenname: Reiko surname: Tsuchiya fullname: Tsuchiya, Reiko organization: Research and Development Dept., SEEMS Inc – sequence: 3 givenname: Nobuyoshi surname: Kosaka fullname: Kosaka, Nobuyoshi organization: From the Division of Molecular and Cellular Medicine, National Cancer Center Research Institute – sequence: 4 givenname: Yusuke surname: Yoshioka fullname: Yoshioka, Yusuke organization: From the Division of Molecular and Cellular Medicine, National Cancer Center Research Institute – sequence: 5 givenname: Kentaro surname: Takagaki fullname: Takagaki, Kentaro organization: Research and Development Dept., SEEMS Inc – sequence: 6 givenname: Katsuyuki surname: Oki fullname: Oki, Katsuyuki organization: Research and Development Dept., SEEMS Inc – sequence: 7 givenname: Fumitaka surname: Takeshita fullname: Takeshita, Fumitaka organization: From the Division of Molecular and Cellular Medicine, National Cancer Center Research Institute – sequence: 8 givenname: Yasuyuki surname: Sakai fullname: Sakai, Yasuyuki organization: Institute of Industrial Science (IIS), The University of Tokyo – sequence: 9 givenname: Masahiko surname: Kuroda fullname: Kuroda, Masahiko organization: Department of Pathology, Tokyo Medical University – sequence: 10 givenname: Takahiro surname: Ochiya fullname: Ochiya, Takahiro organization: From the Division of Molecular and Cellular Medicine, National Cancer Center Research Institute
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23378928$$D View this record in MEDLINE/PubMed
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Snippet	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...
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SubjectTerms	631/378/340 631/45/607/468 631/532/2074 631/61/2297 Adipose tissue Adipose Tissue - cytology Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer's disease Amyloid beta-Peptides - metabolism Bone marrow Cells, Cultured Exosomes Exosomes - metabolism Fluorescent Dyes - chemistry Gene transfer Humanities and Social Sciences Humans Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - metabolism Mesenchymal Stromal Cells - secretion Mesenchyme multidisciplinary Nep gene Neprilysin Neprilysin - genetics Neprilysin - metabolism Neprilysin - secretion Neurodegenerative diseases Peptide Fragments - metabolism Recombinant Proteins - biosynthesis Recombinant Proteins - genetics Science Skin & tissue grafts Stem cells β-Amyloid
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Title	Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes
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