PMID- 30017878
OWN - NLM
STAT- MEDLINE
DCOM- 20190805
LR  - 20190905
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 26
IP  - 9
DP  - 2018 Sep 5
TI  - Extracellular Vesicles Containing IL-4 Modulate Neuroinflammation in a Mouse 
      Model of Multiple Sclerosis.
PG  - 2107-2118
LID - S1525-0016(18)30310-1 [pii]
LID - 10.1016/j.ymthe.2018.06.024 [doi]
AB  - 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.
CI  - Copyright (c) 2018 The American Society of Gene and Cell Therapy. Published by 
      Elsevier Inc. All rights reserved.
FAU - Casella, Giacomo
AU  - Casella G
AD  - Clinical Neuroimmunology Unit, Department of Neuroscience, Institute of 
      Experimental Neurology (InSpe), San Raffaele Scientific Institute, 20132 Milan, 
      Italy.
FAU - Colombo, Federico
AU  - Colombo F
AD  - Clinical Neuroimmunology Unit, Department of Neuroscience, Institute of 
      Experimental Neurology (InSpe), San Raffaele Scientific Institute, 20132 Milan, 
      Italy.
FAU - Finardi, Annamaria
AU  - Finardi A
AD  - Clinical Neuroimmunology Unit, Department of Neuroscience, Institute of 
      Experimental Neurology (InSpe), San Raffaele Scientific Institute, 20132 Milan, 
      Italy.
FAU - Descamps, Helene
AU  - Descamps H
AD  - Neuroimmunology Unit, Department of Neuroscience, Institute of Experimental 
      Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy.
FAU - Ill-Raga, Gerard
AU  - Ill-Raga G
AD  - Clinical Neuroimmunology Unit, Department of Neuroscience, Institute of 
      Experimental Neurology (InSpe), San Raffaele Scientific Institute, 20132 Milan, 
      Italy.
FAU - Spinelli, Antonello
AU  - Spinelli A
AD  - Experimental Imaging Centre, San Raffaele Scientific Institute, 20132 Milan, 
      Italy.
FAU - Podini, Paola
AU  - Podini P
AD  - Department of Neuroscience, Institute of Experimental Neurology, San Raffaele 
      Scientific Institute, 20132 Milan, Italy.
FAU - Bastoni, Mattia
AU  - Bastoni M
AD  - Clinical Neuroimmunology Unit, Department of Neuroscience, Institute of 
      Experimental Neurology (InSpe), San Raffaele Scientific Institute, 20132 Milan, 
      Italy.
FAU - Martino, Gianvito
AU  - Martino G
AD  - Neuroimmunology Unit, Department of Neuroscience, Institute of Experimental 
      Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy.
FAU - Muzio, Luca
AU  - Muzio L
AD  - Neuroimmunology Unit, Department of Neuroscience, Institute of Experimental 
      Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy.
FAU - Furlan, Roberto
AU  - Furlan R
AD  - Clinical Neuroimmunology Unit, Department of Neuroscience, Institute of 
      Experimental Neurology (InSpe), San Raffaele Scientific Institute, 20132 Milan, 
      Italy. Electronic address: furlan.roberto@hsr.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180705
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (CD11b Antigen)
RN  - 207137-56-2 (Interleukin-4)
MH  - Animals
MH  - CD11b Antigen/metabolism
MH  - CD4-Positive T-Lymphocytes/metabolism/ultrastructure
MH  - Cell Line
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Extracellular Vesicles/*metabolism/ultrastructure
MH  - Female
MH  - Interleukin-4/*metabolism
MH  - Macrophages/metabolism/ultrastructure
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Electron, Transmission
MH  - Microscopy, Fluorescence
MH  - Multiple Sclerosis/*metabolism
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC6127510
OTO - NOTNLM
OT  - extracellular vesicles
OT  - neuroinflammation
OT  - phagocytes
EDAT- 2018/07/19 06:00
MHDA- 2019/08/06 06:00
PMCR- 2019/09/05
CRDT- 2018/07/19 06:00
PHST- 2018/03/20 00:00 [received]
PHST- 2018/06/22 00:00 [revised]
PHST- 2018/06/25 00:00 [accepted]
PHST- 2018/07/19 06:00 [pubmed]
PHST- 2019/08/06 06:00 [medline]
PHST- 2018/07/19 06:00 [entrez]
PHST- 2019/09/05 00:00 [pmc-release]
AID - S1525-0016(18)30310-1 [pii]
AID - 10.1016/j.ymthe.2018.06.024 [doi]
PST - ppublish
SO  - Mol Ther. 2018 Sep 5;26(9):2107-2118. doi: 10.1016/j.ymthe.2018.06.024. Epub 2018 
      Jul 5.