The Anti-Apoptotic Effect of ASC-Exosomes in an In Vitro ALS Model and Their Proteomic Analysis

被引:66
作者
Bonafede, Roberta [1 ]
Brandi, Jessica [2 ]
Manfredi, Marcello [3 ,4 ]
Scambi, Ilaria [1 ]
Schiaffino, Lorenzo [1 ]
Merigo, Flavia [1 ]
Turano, Ermanna [1 ]
Bonetti, Bruno [5 ]
Marengo, Emilio [4 ,6 ]
Cecconi, Daniela [2 ]
Mariotti, Raffaella [1 ]
机构
[1] Univ Verona, Dept Neurol Biomed & Movement Sci, I-37134 Verona, Italy
[2] Univ Verona, Dept Biotechnol, I-37134 Verona, Italy
[3] Univ Piemonte Orientale, Dept Translat Med, I-28100 Novara, Italy
[4] Univ Piemonte Orientale, Ctr Translat Res Autoimmune & Allerg Dis, I-15121 Alessandria, Italy
[5] Azienda Osped Univ Integrata Verona, Neurol Unit, I-37126 Verona, Italy
[6] Univ Piemonte Orientale, Dept Sci & Technol Innovat, I-15121 Alessandria, Italy
关键词
extracellular vesicles; proteomic profiling; mesenchymal stem cells; amyotrophic lateral sclerosis; apoptosis; therapy; AMYOTROPHIC-LATERAL-SCLEROSIS; MESENCHYMAL STROMAL CELLS; MOUSE MODEL; STEM-CELLS; SURVIVAL; EXPRESSION; SOD1; DEGENERATION; ANGIOGENESIS; PROTEINS;
D O I
10.3390/cells8091087
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Stem cell therapy represents a promising approach in the treatment of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). The beneficial effect of stem cells is exerted by paracrine mediators, as exosomes, suggesting a possible potential use of these extracellular vesicles as non-cell based therapy. We demonstrated that exosomes isolated from adipose stem cells (ASC) display a neuroprotective role in an in vitro model of ALS. Moreover, the internalization of ASC-exosomes by the cells was shown and the molecules and the mechanisms by which exosomes could exert their beneficial effect were addressed. We performed for the first time a comprehensive proteomic analysis of exosomes derived from murine ASC. We identified a total of 189 proteins and the shotgun proteomics analysis revealed that the exosomal proteins are mainly involved in cell adhesion and negative regulation of the apoptotic process. We correlated the protein content to the anti-apoptotic effect of exosomes observing a downregulation of pro-apoptotic proteins Bax and cleaved caspase-3 and upregulation of anti-apoptotic protein Bcl-2 alpha, in an in vitro model of ALS after cell treatment with exosomes. Overall, this study shows the neuroprotective effect of ASC-exosomes after their internalization and their global protein profile, that could be useful to understand how exosomes act, demonstrating that they can be employed as therapy in neurodegenerative diseases.
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页数:20
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共 49 条
[31]  
Martin LJ, 2000, INT J MOL MED, V5, P3
[32]   HMGB1 Osteo-Modulatory Action on Osteosarcoma SaOS-2 Cell Line: An Integrated Study From Biochemical and -Omics Approaches [J].
Martinotti, Simona ;
Patrone, Mauro ;
Manfredi, Marcello ;
Gosetti, Fabio ;
Pedrazzi, Marco ;
Marengo, Emilio ;
Ranzato, Elia .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2016, 117 (11) :2559-2569
[33]   Stem cell therapy in amyotrophic lateral sclerosis [J].
Meamar, Rokhsareh ;
Nasr-Esfahani, Mohammad Hossein ;
Mousavi, Seyed Ali ;
Basiri, Keivan .
JOURNAL OF CLINICAL NEUROSCIENCE, 2013, 20 (12) :1659-1663
[34]   Insights into the role of ribonuclease 4 polymorphisms in amyotrophic lateral sclerosis [J].
Padhi, Aditya K. ;
Narain, Priyam ;
Dave, Upma ;
Satija, Rohit ;
Patir, Anirudh ;
Gomes, James .
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2019, 37 (01) :116-130
[35]   Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria [J].
Pasinelli, P ;
Belford, ME ;
Lennon, N ;
Bacskai, BJ ;
Hyman, BT ;
Trotti, D ;
Brown, RH .
NEURON, 2004, 43 (01) :19-30
[36]   Stem molecular signature of adipose-derived stromal cells [J].
Peroni, Daniele ;
Scambi, Ilaria ;
Pasini, Annalisa ;
Lisi, Veronica ;
Bifari, Francesco ;
Krampera, Mauro ;
Rigotti, Gino ;
Sbarbati, Andrea ;
Galie, Mirco .
EXPERIMENTAL CELL RESEARCH, 2008, 314 (03) :603-615
[37]   IFNγ-stimulated dendritic cell exosomes as a potential therapeutic for remyelination [J].
Pusic, Aya D. ;
Pusic, Kae M. ;
Clayton, Benjamin L. L. ;
Kraig, Richard P. .
JOURNAL OF NEUROIMMUNOLOGY, 2014, 266 (1-2) :12-23
[38]   Mutation of SOD1 in ALS: a gain of a loss of function [J].
Sau, Daniela ;
De Biasi, Silvia ;
Vitellaro-Zuccarello, Laura ;
Riso, Patrizia ;
Guarnieri, Serena ;
Porrini, Marisa ;
Simeoni, Silvia ;
Crippa, Valeria ;
Onesto, Elisa ;
Palazzolo, Isabella ;
Rusmini, Paola ;
Bolzoni, Elena ;
Bendotti, Caterina ;
Poletti, Angelo .
HUMAN MOLECULAR GENETICS, 2007, 16 (13) :1604-1618
[39]   STRING v10: protein-protein interaction networks, integrated over the tree of life [J].
Szklarczyk, Damian ;
Franceschini, Andrea ;
Wyder, Stefan ;
Forslund, Kristoffer ;
Heller, Davide ;
Huerta-Cepas, Jaime ;
Simonovic, Milan ;
Roth, Alexander ;
Santos, Alberto ;
Tsafou, Kalliopi P. ;
Kuhn, Michael ;
Bork, Peer ;
Jensen, Lars J. ;
von Mering, Christian .
NUCLEIC ACIDS RESEARCH, 2015, 43 (D1) :D447-D452
[40]   Inhibition of IGF-1 Signalling Enhances the Apoptotic Effect of AS602868, an IKK2 Inhibitor, in Multiple Myeloma Cell Lines [J].
Tagoug, Ines ;
De Chalon, Amelie Sauty ;
Dumontet, Charles .
PLOS ONE, 2011, 6 (07)