Extracellular vesicles from adipose mesenchymal stem cells target inflamed lymph nodes in experimental autoimmune encephalomyelitis.

Autor: Turano E; Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy., Scambi I; Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy., Bonafede R; Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy., Dusi S; Division of General Pathology, Department of Medicine, University of Verona, Verona, Italy., Angelini G; Division of General Pathology, Department of Medicine, University of Verona, Verona, Italy., Lopez N; Division of General Pathology, Department of Medicine, University of Verona, Verona, Italy., Marostica G; Clinical Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy., Rossi B; Division of General Pathology, Department of Medicine, University of Verona, Verona, Italy., Furlan R; Clinical Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy., Constantin G; Division of General Pathology, Department of Medicine, University of Verona, Verona, Italy., Mariotti R; Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy., Bonetti B; Neurology Unit, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy. Electronic address: bruno.bonetti@aovr.veneto.it.
Jazyk: angličtina
Zdroj: Cytotherapy [Cytotherapy] 2024 Mar; Vol. 26 (3), pp. 276-285. Date of Electronic Publication: 2024 Jan 16.
DOI: 10.1016/j.jcyt.2023.12.007
Abstrakt: Background Aims: Adipose mesenchymal stem cells (ASCs) represent a promising therapeutic approach in inflammatory neurological disorders, including multiple sclerosis (MS). Recent lines of evidence indicate that most biological activities of ASCs are mediated by the delivery of soluble factors enclosed in extracellular vesicles (EVs). Indeed, we have previously demonstrated that small EVs derived from ASCs (ASC-EVs) ameliorate experimental autoimmune encephalomyelitis (EAE), a murine model of MS. The precise mechanisms and molecular/cellular target of EVs during EAE are still unknown.
Methods: To investigate the homing of ASC-EVs, we intravenously injected small EVs loaded with ultra-small superparamagnetic iron oxide nanoparticles (USPIO) at disease onset in EAE-induced C57Bl/6J mice. Histochemical analysis and transmission electron microscopy were carried out 48 h after EV treatment. Moreover, to assess the cellular target of EVs, flow cytometry on cells extracted ex vivo from EAE mouse lymph nodes was performed.
Results: Histochemical and ultrastructural analysis showed the presence of labeled EVs in lymph nodes but not in lungs and spinal cord of EAE injected mice. Moreover, we identified the cellular target of EVs in EAE lymph nodes by flow cytometry: ASC-EVs were preferentially located in macrophages, with a consistent amount also noted in dendritic cells and CD4+ T lymphocytes.
Conclusions: This represents the first direct evidence of the privileged localization of ASC-EVs in draining lymph nodes of EAE after systemic injection. These data provide prominent information on the distribution, uptake and retention of ASC-EVs, which may help in the development of EV-based therapy in MS.
Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article.
(Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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