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Mesenchymal stem cells enhance α-synuclein clearance via M2 microglia polarization in experimental and human parkinsonian disorder
DC Field | Value | Language |
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dc.contributor.author | 이필휴 | - |
dc.date.accessioned | 2017-10-26T07:43:29Z | - |
dc.date.available | 2017-10-26T07:43:29Z | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 0001-6322 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/152428 | - |
dc.description.abstract | Microglia in the brain show distinctive phenotypes that serve different functions. In particular, M2-polarized microglia are anti-inflammatory and phagocytic cells that serve a restorative function. In this study, we investigated whether mesenchymal stem cells (MSCs) enhance the phagocytic clearance of α-synuclein via M2 microglia polarization, and thereby exert neuroprotective effects in α-synuclein-enriched experimental models and patients with multiple system atrophy (MSA). Treatment of BV2 cells with α-synuclein induced an inflammatory phenotype, whereas co-culture of α-synuclein-treated BV2 cells with MSCs induced an anti-inflammatory M2 phenotype, with decreased α-synuclein levels and increased lysosomal activity, leading to greater viability of neuronal cells co-cultured with BV2 cells. Using IL-4 receptor siRNA in BV2 cells and IL-4 siRNA in MSCs, we found that M2 microglia polarization was induced by IL-4 secreted from MSCs. In α-synuclein-inoculated mice, MSC treatment induced M2 microglia polarization decreased α-synuclein levels, and had a prosurvival effect on neurons. Using IL-4 and IL-4 receptor knockout mice, we further confirmed that IL-4 secreted from MSCs induced phagocytic clearance of α-synuclein through M2 microglia polarization. Next, we found that the cerebrospinal fluid (CSF) from MSC-transplanted MSA patients induced microglia M2 polarization and had a prosurvival effect via enhanced clearance of α-synuclein in α-synuclein-treated BV2 cells. Finally, a serial CSF study demonstrated that changes in oligomeric α-synuclein from baseline to 1-year follow-up were greater in the CSF of MSC-transplanted MSA patients than in placebo-transplanted MSA patients. These findings indicate that MSCs exert a neuroprotective effect via the clearance of extracellular α-synuclein by controlling microglia M2 polarization, suggesting that MSCs could be used as a disease-modifying therapy for patients with α-synucleinopathies. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.publisher | Springer Verlag | - |
dc.relation.isPartOf | ACTA NEUROPATHOLOGICA | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Anti-Inflammatory Agents/pharmacology* | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | Cell Polarity/drug effects | - |
dc.subject.MESH | Coculture Techniques | - |
dc.subject.MESH | Cytokines/genetics | - |
dc.subject.MESH | Cytokines/metabolism | - |
dc.subject.MESH | Disease Models, Animal | - |
dc.subject.MESH | Gene Expression Regulation/drug effects | - |
dc.subject.MESH | Gene Expression Regulation/genetics | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Interleukin-4/pharmacology | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Mesenchymal Stromal Cells/drug effects | - |
dc.subject.MESH | Mesenchymal Stromal Cells/physiology* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | Mice, Knockout | - |
dc.subject.MESH | Microglia/drug effects | - |
dc.subject.MESH | Microglia/physiology* | - |
dc.subject.MESH | Multiple System Atrophy/surgery | - |
dc.subject.MESH | Neuroprotective Agents/pharmacology | - |
dc.subject.MESH | Parkinsonian Disorders/pathology* | - |
dc.subject.MESH | Phosphopyruvate Hydratase/genetics | - |
dc.subject.MESH | Phosphopyruvate Hydratase/metabolism | - |
dc.subject.MESH | alpha-Synuclein/metabolism | - |
dc.subject.MESH | alpha-Synuclein/pharmacology* | - |
dc.title | Mesenchymal stem cells enhance α-synuclein clearance via M2 microglia polarization in experimental and human parkinsonian disorder | - |
dc.type | Article | - |
dc.publisher.location | Germany | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Neurology | - |
dc.contributor.googleauthor | Hyun Jung Park | - |
dc.contributor.googleauthor | Se Hee Oh | - |
dc.contributor.googleauthor | Ha Na Kim | - |
dc.contributor.googleauthor | Yu Ju Jung | - |
dc.contributor.googleauthor | Phil Hyu Lee | - |
dc.identifier.doi | 10.1007/s00401-016-1605-6 | - |
dc.contributor.localId | A03270 | - |
dc.relation.journalcode | J00021 | - |
dc.identifier.eissn | 1432-0533 | - |
dc.identifier.pmid | 27497943 | - |
dc.identifier.url | https://link.springer.com/article/10.1007%2Fs00401-016-1605-6 | - |
dc.subject.keyword | IL-4 | - |
dc.subject.keyword | M2-polarized microglia | - |
dc.subject.keyword | Mesenchymal stem cells | - |
dc.subject.keyword | α-Synuclein | - |
dc.contributor.alternativeName | Lee, Phil Hyu | - |
dc.contributor.affiliatedAuthor | Lee, Phil Hyu | - |
dc.citation.volume | 132 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 685 | - |
dc.citation.endPage | 701 | - |
dc.identifier.bibliographicCitation | ACTA NEUROPATHOLOGICA, Vol.132(5) : 685-701, 2016 | - |
dc.date.modified | 2017-10-24 | - |
dc.identifier.rimsid | 48635 | - |
dc.type.rims | ART | - |
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