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Open AccessArticle

ASC-Exosomes Ameliorate the Disease Progression in SOD1(G93A) Murine Model Underlining Their Potential Therapeutic Use in Human ALS

1
Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy
2
Department of Computer Sciences, University of Verona, 37134 Verona, Italy
3
Neurology Unit, Azienda Ospedaliera Universitaria Integrata Verona, 37126 Verona, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3651; https://doi.org/10.3390/ijms21103651
Received: 27 March 2020 / Revised: 16 May 2020 / Accepted: 19 May 2020 / Published: 21 May 2020
(This article belongs to the Special Issue Applications of Mesenchymal Stem Cells in Neuroscience)
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motoneurons. To date, there is no effective treatment available. Exosomes are extracellular vesicles that play important roles in intercellular communication, recapitulating the effect of origin cells. In this study, we tested the potential neuroprotective effect of exosomes isolated from adipose-derived stem cells (ASC-exosomes) on the in vivo model most widely used to study ALS, the human SOD1 gene with a G93A mutation (SOD1(G93A)) mouse. Moreover, we compared the effect of two different routes of exosomes administration, intravenous and intranasal. The effect of exosomes administration on disease progression was monitored by motor tests and analysis of lumbar motoneurons and glial cells, neuromuscular junction, and muscle. Our results demonstrated that repeated administration of ASC-exosomes improved the motor performance; protected lumbar motoneurons, the neuromuscular junction, and muscle; and decreased the glial cells activation in treated SOD1(G93A) mice. Moreover, exosomes have the ability to home to lesioned ALS regions of the animal brain. These data contribute by providing additional knowledge for the promising use of ASC-exosomes as a therapy in human ALS. View Full-Text
Keywords: amyotrophic lateral sclerosis; stem cells; extracellular vesicles; motoneurons; neuromuscular junction; homing; MRI amyotrophic lateral sclerosis; stem cells; extracellular vesicles; motoneurons; neuromuscular junction; homing; MRI
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Bonafede, R.; Turano, E.; Scambi, I.; Busato, A.; Bontempi, P.; Virla, F.; Schiaffino, L.; Marzola, P.; Bonetti, B.; Mariotti, R. ASC-Exosomes Ameliorate the Disease Progression in SOD1(G93A) Murine Model Underlining Their Potential Therapeutic Use in Human ALS. Int. J. Mol. Sci. 2020, 21, 3651.

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