scholarly journals MiR-219a-5p Enriched Extracellular Vesicles Induce OPC Differentiation and EAE Improvement More Efficiently Than Liposomes and Polymeric Nanoparticles

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 186 ◽  
Author(s):  
Iñaki Osorio-Querejeta ◽  
Susana Carregal-Romero ◽  
Ana Ayerdi-Izquierdo ◽  
Imre Mäger ◽  
Leslie A. Nash ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cell Differentiation ◽  
Extracellular Vesicles ◽  
Polymeric Nanoparticles ◽  
Plga Nanoparticles ◽  
Precursor Cell ◽  
Oligodendrocyte Precursor Cell ◽  
Promising Tool ◽  
Oligodendrocyte Precursor ◽  
Multiple Sclerosis Patients

Remyelination is a key aspect in multiple sclerosis pathology and a special effort is being made to promote it. However, there is still no available treatment to regenerate myelin and several strategies are being scrutinized. Myelination is naturally performed by oligodendrocytes and microRNAs have been postulated as a promising tool to induce oligodendrocyte precursor cell differentiation and therefore remyelination. Herein, DSPC liposomes and PLGA nanoparticles were studied for miR-219a-5p encapsulation, release and remyelination promotion. In parallel, they were compared with biologically engineered extracellular vesicles overexpressing miR-219a-5p. Interestingly, extracellular vesicles showed the highest oligodendrocyte precursor cell differentiation levels and were more effective than liposomes and polymeric nanoparticles crossing the blood–brain barrier. Finally, extracellular vesicles were able to improve EAE animal model clinical evolution. Our results indicate that the use of extracellular vesicles as miR-219a-5p delivery system can be a feasible and promising strategy to induce remyelination in multiple sclerosis patients.

scholarly journals Co-Ultramicronized Palmitoylethanolamide/Luteolin-Induced Oligodendrocyte Precursor Cell Differentiation is Associated With Tyro3 Receptor Upregulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Facci ◽  
Massimo Barbierato ◽  
Mariella Fusco ◽  
Pietro Giusti ◽  
Morena Zusso
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Cell Differentiation ◽  
Neuronal Degeneration ◽  
Precursor Cell ◽  
Myelin Proteins ◽  
Oligodendrocyte Precursor Cell ◽  
Tam Receptors ◽  
Oligodendrocyte Precursor

Remyelination in patients with multiple sclerosis frequently fails, especially in the chronic phase of the disease promoting axonal and neuronal degeneration and progressive disease disability. Drug-based therapies able to promote endogenous remyelination capability of oligodendrocytes are thus emerging as primary approaches to multiple sclerosis. We have recently reported that the co-ultramicronized composite of palmitoylethanolamide and the flavonoid luteolin (PEALut) promotes oligodendrocyte precursor cell (OPC) maturation without affecting proliferation. Since TAM receptor signaling has been reported to be important modulator of oligodendrocyte survival, we here evaluated the eventual involvement of TAM receptors in PEALut-induced OPC maturation. The mRNAs related to TAM receptors -Tyro3, Axl, and Mertk- were all present at day 2 in vitro. However, while Tyro3 gene expression significantly increased upon cell differentiation, Axl and Mertk did not change during the first week in vitro. Tyro3 gene expression developmental pattern resembled that of MBP myelin protein. In OPCs treated with PEALut the developmental increase of Tyro3 mRNA was significantly higher as compared to vehicle while was reduced gene expression related to Axl and Mertk. Rapamycin, an inhibitor of mTOR, prevented oligodendrocyte growth differentiation and myelination. PEALut, administered to the cultures 30 min after rapamycin, prevented the alteration of mRNA basal expression of the TAM receptors as well as the expression of myelin proteins MBP and CNPase. Altogether, data obtained confirm that PEALut promotes oligodendrocyte differentiation as shown by the increase of MBP and CNPase and Tyro3 mRNAs as well as CNPase and Tyro3 immunostainings. The finding that these effects are reduced when OPCs are exposed to rapamycin suggests an involvement of mTOR signaling in PEALut effects.

scholarly journals Inhibition of phosphodiesterase‐4 promotes oligodendrocyte precursor cell differentiation and enhances CNS remyelination

2013 ◽  
Vol 5 (12) ◽  
pp. 1918-1934 ◽  
Author(s):  
Yasir A. Syed ◽  
Alexandra Baer ◽  
Matthias P. Hofer ◽  
Ginez A. González ◽  
Jon Rundle ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Precursor Cell ◽  
Oligodendrocyte Precursor Cell ◽  
Phosphodiesterase 4 ◽  
Oligodendrocyte Precursor

scholarly journals Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice

2019 ◽  
Vol 35 (3) ◽  
pp. 434-446 ◽  
Author(s):  
Fengfeng Lu ◽  
Dou Yin ◽  
Yingyan Pu ◽  
Weili Liu ◽  
Zhenghao Li ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Shikimic Acid ◽  
Precursor Cell ◽  
Oligodendrocyte Precursor Cell ◽  
Oligodendrocyte Precursor

scholarly journals Full-Length and Fragmented Netrin-1 in Multiple Sclerosis Plaques Are Inhibitors of Oligodendrocyte Precursor Cell Migration

2013 ◽  
Vol 183 (3) ◽  
pp. 673-680 ◽  
Author(s):  
Jenea M. Bin ◽  
Sathyanath Rajasekharan ◽  
Tanja Kuhlmann ◽  
Ilana Hanes ◽  
Nathalie Marcal ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cell Migration ◽  
Precursor Cell ◽  
Full Length ◽  
Oligodendrocyte Precursor Cell ◽  
Oligodendrocyte Precursor

scholarly journals Signaling via Immunoglobulin Fc Receptors Induces Oligodendrocyte Precursor Cell Differentiation

2003 ◽  
Vol 4 (6) ◽  
pp. 841-852 ◽  
Author(s):  
Jin Nakahara ◽  
Kyoko Tan-Takeuchi ◽  
Chika Seiwa ◽  
Mari Gotoh ◽  
Tomonori Kaifu ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Fc Receptors ◽  
Precursor Cell ◽  
Oligodendrocyte Precursor Cell ◽  
Oligodendrocyte Precursor

scholarly journals Inactivation of LCN2/EGR1 Promotes Oligodendrocyte Progenitor Cell Differentiation and Remyelination after White Matter Injury

2020 ◽  
Author(s):  
Qiang Li ◽  
Xufang Ru ◽  
Yang Yang ◽  
Hengli Zhao ◽  
Jie Qu ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
White Matter ◽  
Growth Response ◽  
Early Growth ◽  
Precursor Cell ◽  
White Matter Injury ◽  
Lipocalin 2 ◽  
Oligodendrocyte Precursor Cell ◽  
Early Growth Response ◽  
Oligodendrocyte Precursor

AbstractThe insufficient remyelination due to the impaired oligodendrocyte precursor cell differentiation and maturation is highly associated with irreversible white matter injury and neurological deficits. Consequently, inhibitory components and microenvironment for remyelination might serve as potential therapeutic targets for treating white matter injury after acute central nervous system injury and neurodegeneration diseases. Lipocalin-2 was recently reported to corelate with white matter in both atypical, acute white matter injured disease subarachnoid hemorrhage and typical, chronic white matter injured disease multiple sclerosis. To elucidate the role and underlying mechanism of Lipocalin-2 in oligodendrocyte precursor cell differentiation and remyelination, we used genetic inhibition and a constitutive conditional knockout model with subarachnoid hemorrhage or multiple sclerosis. We found that the genetic inhibition of the increase in Lipocalin-2 promoted oligodendrocyte precursor cell differentiation, remyelination, and functional recovery after subarachnoid hemorrhage or multiple sclerosis. Unexpectedly, the inhibition of Lipocalin-2 did not reduce glial activation and inflammation. Lipocalin-2 was shown to activate Early Growth Response Protein 1 in oligodendrocyte precursor cells, which is partly regulated by its receptor SLC22A17. In the conditional knockout of Early Growth Response Protein 1 in oligodendrocyte precursor cells, we discovered enhanced oligodendrocyte precursor cell differentiation in developing and injured white matter; consistently, the specific inactivation of Early Growth Response Protein 1 promoted remyelination and neurological recovery after subarachnoid hemorrhage or multiple sclerosis. Thus, we propose that following white matter injury in humans, the increase in Lipocalin-2 activates Early Growth Response Protein 1 and consequently impair oligodendrocyte precursor cell differentiation and myelin repair. Our results suggest that therapies specifically inactivating Lipocalin-2/ Early Growth Response Protein 1 signal in oligodendroglial lineage cells could represent a novel strategy to enhance differentiation and remyelination in white matter injury patients.

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