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Open AccessArticle

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

1
Department of Neurological, Biomedical and Movement Science, University of Verona, 37134 Verona, Italy
2
Department of Biotechnology, University of Verona, 37134 Verona, Italy
3
Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy
4
Center for Translational Research on Autoimmune and Allergic Diseases, University of Piemonte Orientale, Italy
5
Neurology Unit, Azienda Ospedaliera Universitaria Integrata Verona, 37126 Verona, Italy
6
Department of Sciences and Technological Innovation, University of Piemonte Orientale, Alessandria, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(9), 1087; https://doi.org/10.3390/cells8091087
Received: 23 July 2019 / Revised: 5 September 2019 / Accepted: 12 September 2019 / Published: 14 September 2019
(This article belongs to the Special Issue Therapeutic Applications of Extracellular Vesicles)
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 α, 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. View Full-Text
Keywords: extracellular vesicles; proteomic profiling; mesenchymal stem cells; amyotrophic lateral sclerosis; apoptosis; therapy extracellular vesicles; proteomic profiling; mesenchymal stem cells; amyotrophic lateral sclerosis; apoptosis; therapy
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Bonafede, R.; Brandi, J.; Manfredi, M.; Scambi, I.; Schiaffino, L.; Merigo, F.; Turano, E.; Bonetti, B.; Marengo, E.; Cecconi, D.; Mariotti, R. The Anti-Apoptotic Effect of ASC-Exosomes in an In Vitro ALS Model and Their Proteomic Analysis. Cells 2019, 8, 1087.

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