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

被引:434
作者
Katsuda, Takeshi [1 ,2 ]
Tsuchiya, Reiko [3 ]
Kosaka, Nobuyoshi [1 ]
Yoshioka, Yusuke [1 ]
Takagaki, Kentaro [3 ]
Oki, Katsuyuki [3 ]
Takeshita, Fumitaka [1 ]
Sakai, Yasuyuki [2 ]
Kuroda, Masahiko [4 ]
Ochiya, Takahiro [1 ]
机构
[1] Natl Canc Ctr, Div Mol & Cellular Med, Chuo Ku, Tokyo 1040045, Japan
[2] Univ Tokyo, IIS, Meguro Ku, Tokyo 1538505, Japan
[3] SEEMS Inc, Res & Dev Dept, Koto Ku, Tokyo 1350064, Japan
[4] Tokyo Med Univ, Dept Pathol, Shinjuku Ku, Tokyo 1608402, Japan
来源
SCIENTIFIC REPORTS | 2013年 / 3卷
关键词
AMYLOID-BETA; A-BETA; BRAIN; VESICLES; TRANSPLANTATION; IDENTIFICATION; MICRORNAS; PATHWAY; MODEL; MICE;
D O I
10.1038/srep01197
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Alzheimer's disease (AD) is characterized by the accumulation of beta-amyloid peptide (Ab) in the brain because of an imbalance between A beta production and clearance. Neprilysin (NEP) is the most important A beta-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 mu g protein from ADSC-derived exosomes was equivalent to that of similar to 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 A beta 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.
引用
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页数:11
相关论文
共 46 条
[1]   Comparative Analysis of Chemokine Receptor's Expression in Mesenchymal Stem Cells Derived from Human Bone Marrow and Adipose Tissue [J].
Ahmadian Kia, Naghmeh ;
Bahrami, Ahmad Reza ;
Ebrahimi, Marzieh ;
Matin, Maryam M. ;
Neshati, Zeinab ;
Almohaddesin, Mahmood Rais ;
Aghdami, Naser ;
Bidkhori, Hamid Reza .
JOURNAL OF MOLECULAR NEUROSCIENCE, 2011, 44 (03) :178-185
[2]   Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes [J].
Alvarez-Erviti, Lydia ;
Seow, Yiqi ;
Yin, HaiFang ;
Betts, Corinne ;
Lakhal, Samira ;
Wood, Matthew J. A. .
NATURE BIOTECHNOLOGY, 2011, 29 (04) :341-U179
[3]   IFATS Collection: In Vivo Therapeutic Potential of Human Adipose Tissue Mesenchymal Stem Cells After Transplantation into Mice with Liver Injury [J].
Banas, Agnieszka ;
Teratani, Takumi ;
Yamamoto, Yusuke ;
Tokuhara, Makoto ;
Takeshita, Fumitaka ;
Osaki, Mitsuhiko ;
Kawamata, Masaki ;
Kato, Takashi ;
Okochi, Hitoshi ;
Ochiya, Takahiro .
STEM CELLS, 2008, 26 (10) :2705-2712
[4]   Stem cell plasticity: Learning from hepatogenic differentiation strategies [J].
Banas, Agnieszka ;
Yamamoto, Yusuke ;
Teratani, Takumi ;
Ochiya, Takahiro .
DEVELOPMENTAL DYNAMICS, 2007, 236 (12) :3228-3241
[5]   Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes [J].
Banas, Agnieszka ;
Teratani, Takumi ;
Yamamoto, Yusuke ;
Tokuhara, Makoto ;
Takeshita, Fumitaka ;
Quinn, Gary ;
Okochi, Hitoshi ;
Ochiya, Takahiro .
HEPATOLOGY, 2007, 46 (01) :219-228
[6]   Mesenchymal Stem Cell-Derived Microvesicles Protect Against Acute Tubular Injury [J].
Bruno, Stefania ;
Grange, Cristina ;
Deregibus, Maria Chiara ;
Calogero, Raffaele A. ;
Saviozzi, Silvia ;
Collino, Federica ;
Morando, Laura ;
Busca, Alessandro ;
Falda, Michele ;
Bussolati, Benedetta ;
Tetta, Ciro ;
Camussi, Giovanni .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2009, 20 (05) :1053-1067
[7]   Characteristics of human prostasomes isolated from three different sources [J].
Carlsson, L ;
Nilsson, O ;
Larsson, A ;
Stridsberg, M ;
Sahlén, G ;
Ronquist, G .
PROSTATE, 2003, 54 (04) :322-330
[8]   Concise review: Mesenchymal stem cells: Their phenotype, differentiation capacity, immunological features, and potential for homing [J].
Chamberlain, Giselle ;
Fox, James ;
Ashton, Brian ;
Middleton, Jim .
STEM CELLS, 2007, 25 (11) :2739-2749
[9]   Shedding microvesicles: artefacts no more [J].
Cocucci, Emanuele ;
Racchetti, Gabriella ;
Meldolesi, Jacopo .
TRENDS IN CELL BIOLOGY, 2009, 19 (02) :43-51
[10]   Candidate biomarkers in exosome-like vesicles purified from rat and mouse urine samples [J].
Conde-Vancells, Javier ;
Rodriguez-Suarez, Eva ;
Gonzalez, Esperanza ;
Berisa, Agustin ;
Gil, David ;
Embade, Nieves ;
Valle, Mikel ;
Luka, Zigmund ;
Elortza, Felix ;
Wagner, Conrad ;
Lu, Shelly C. ;
Mato, Jose M. ;
Falcon-Perez, Juan M. .
PROTEOMICS CLINICAL APPLICATIONS, 2010, 4 (04) :416-425