https://doi.org/10.4081/ejh.2024.4040

Adipose mesenchymal stem cells-derived extracellular vesicles exert their preferential action in damaged central sites of SOD1 mice rather than peripherally

Vol. 68 No. 3 (2024)
Submitted: 19 April 2024
Accepted: 10 June 2024
Published: 4 July 2024
Amyotrophic lateral sclerosis, extracellular vesicles, adipose-derived stem cells, exosomes, SOD1(G93A) mice, neuroprotection, motoneurons
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Authors

Ermanna Turano
ermanna.turano@univr.it
https://orcid.org/0000-0002-0760-1787
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy.
Federica Virla
https://orcid.org/0009-0001-7346-9139
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy.
Ilaria Scambi
https://orcid.org/0000-0002-7678-6359
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy.
Sylwia Dabrowska
https://orcid.org/0000-0002-0758-8703
NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
Oluwamolakun Bankole
https://orcid.org/0000-0003-3374-0614
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Alberta, Canada.
Raffaella Mariotti
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder involving motor neuron (MN) loss in the motor cortex, brainstem and spinal cord leading to progressive paralysis and death. Due to the pathogenetic complexity, there are no effective therapies available. In this context the use of mesenchymal stem cells and their vesicular counterpart is an emerging therapeutic strategy to counteract neurodegeneration. The extracellular vesicles derived from adipose stem cells (ASC-EVs) recapitulate and ameliorate the neuroprotective effect of stem cells and, thanks to their small dimensions, makes their use suitable to develop novel therapeutic approaches for neurodegenerative diseases as ALS. Here we investigate a therapeutic regimen of ASC-EVs injection in SOD1(G93A) mice, the most widely used murine model of ALS. Repeated intranasal administrations of high doses of ASC-EVs were able to ameliorate motor performance of injected SOD1(G93A) mice at the early stage of the disease and produce a significant improvement at the end-stage in the lumbar MNs rescue. Moreover, ASC-EVs preserve the structure of neuromuscular junction without counteracting the muscle atrophy. The results indicate that the intranasal ASC-EVs administration acts in central nervous system sites rather than at peripheral level in SOD1(G93A) mice. These considerations allow us to identify future applications of ASC-EVs that involve different targets simultaneously to maximize the clinical and neuropathological outcomes in ALS in vivo models.

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Ethics Approval

the study was approved by the University of Verona Committee on Animal Research and by the Italian Ministry of Health (ministerial authorization number 56DC9.72)

Supporting Agencies

Polish National Agency for Academic Exchange
Sylwia Dabrowska, NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy

How to Cite

Turano, E., Virla, F., Scambi, I., Dabrowska, S., Bankole, O., & Mariotti, R. (2024). Adipose mesenchymal stem cells-derived extracellular vesicles exert their preferential action in damaged central sites of SOD1 mice rather than peripherally. European Journal of Histochemistry, 68(3). https://doi.org/10.4081/ejh.2024.4040
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