Cited by 134Extracellular vesicles in diseaseMultiple Sclerosis Research StudiesNanoparticle-Based Drug Delivery

Extracellular Vesicles Containing IL-4 Modulate Neuroinflammation in a Mouse Model of Multiple Sclerosis

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Casella, Giacomo, Colombo, Federico, Finardi, Annamaria, Descamps, Hélène, Ill-Raga, Gerard, Spinelli, Antonello, Podini, Paola, Bastoni, Mattia +3 more·2018·Molecular Therapy

Abstract

Extracellular vesicles (EVs) play a major role in cell-to-cell communication in physiological and pathological conditions, and their manipulation may represent a promising therapeutic strategy. Microglia, the parenchymal mononuclear phagocytes of the brain, modulate neighboring cells also through the release of EVs. The production of custom EVs filled with desired molecules, possibly targeted to make their uptake cell specific, and their administration in biological fluids may represent a valid approach for drug delivery. We engineered a murine microglia cell line, BV-2, to release EVs overexpressing the endogenous "eat me" signal Lactadherin (Mfg-e8) on the surface to target phagocytes and containing the anti-inflammatory cytokine IL-4. A single injection of 10 7 IL-4 + Mfg-e8 + EVs into the cisterna magna modulated established neuroinflammation and significantly reduced clinical signs in the mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Injected IL-4 + Mfg-e8 + EVs target mainly phagocytes (i.e., macrophages and microglia) surrounding liquoral spaces, and their cargo promote the upregulation of anti-inflammatory markers chitinase 3-like 3 (ym1) and arginase-1 (arg1), significantly reducing tissue damage. Engineered EVs may represent a biological drug delivery tool able to deliver multiple functional molecules simultaneously to treat neuroinflammatory diseases.

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Crossref · 10.1016/j.ymthe.2018.06.024

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Authors
Casella, G., Colombo, F., Finardi, A., Descamps, H., Ill-Raga, G., Spinelli, A., Podini, P., Bastoni, M., Martino, G., Muzio, L., & Furlan, R.
Affiliations
IRCCS Ospedale San Raffaele (IT)
Corresponding author
Furlan, Roberto
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2018-09
Volume
26
Issue
9
Pages
2107-2118
ISSN
1525-0016 (ISSN-L)
OpenAlex
W2814481017
Cited by
134
References
41
Citations by year
2026: 8 · 2025: 18 · 2024: 22 · 2023: 17 · 2022: 22 · 2021: 23 · 2020: 17 · 2019: 5 · 2018: 1 · 2016: 1
FWCI
4.09
Type
journal article
Language
en
Open access
Locations
  • Molecular Therapy (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
Funders
  • Fondazione Italiana Sclerosi Multipla – FISM (2010/R/20)
  • Merck
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
extracellular vesicles, IL-4, neuroinflammation, multiple sclerosis, experimental autoimmune encephalomyelitis, microglia, MFG-E8, lactadherin, BV-2 cells, engineered vesicles, drug delivery, anti-inflammatory cytokines, Ym1, arginase-1, macrophages
MeSH terms
Extracellular Vesicles, Animals, Cell Line, Cells, Cultured, Disease Models, Animal, Female, Macrophages, Mice, Inbred C57BL, Microscopy, Fluorescence, Multiple Sclerosis, CD4-Positive T-Lymphocytes, Interleukin-4, Reverse Transcriptase Polymerase Chain Reaction, CD11b Antigen, Microscopy, Electron, Transmission, Mice, Rats

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