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Microvesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells as a New Protective Strategy in Osteoarthritic Chondrocytes

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Microvesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells as a New Protective Strategy in Osteoarthritic Chondrocytes

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dc.contributor.author Tofiño-Vian, Miguel es_ES
dc.contributor.author Guillen Salazar, Mª Isabel es_ES
dc.contributor.author Perez del Caz, M.D. es_ES
dc.contributor.author Silvestre, A. es_ES
dc.contributor.author Alcaraz Tormo, Mª Jose es_ES
dc.date.accessioned 2019-02-28T21:00:26Z
dc.date.available 2019-02-28T21:00:26Z
dc.date.issued 2018 es_ES
dc.identifier.issn 1015-8987 es_ES
dc.identifier.uri http://hdl.handle.net/10251/117448
dc.description.abstract [EN] Background/Aims: Chronic inflammation contributes to cartilage degeneration during the progression of osteoarthritis (OA). Adipose tissue-derived mesenchymal stem cells (ADMSC) show great potential to treat inflammatory and degradative processes in OA and have demonstrated paracrine effects in chondrocytes. In the present work, we have isolated and characterized the extracellular vesicles from human AD-MSC to investigate their role in the chondroprotective actions of these cells. Methods: AD-MSC were isolated by collagenase treatment from adipose tissue from healthy individuals subjected to abdominal lipectomy surgery. Microvesicles and exosomes were obtained from conditioned medium by filtration and differential centrifugation. Chondrocytes from OA patients were used in primary culture and stimulated with 10 ng/ml interleukin(IL)-1 beta in the presence or absence of AD-MSC microvesicles, exosomes or conditioned medium. Protein expression was investigated by ELISA and immunofluorescence, transcription factor-DNA binding by ELISA, gene expression by real-time PCR, prostaglandin E-2 (PGE(2)) by radioimmunoassay, and matrix metalloproteinase (MMP) activity and nitric oxide (NO) production by fluorometry. Results: In OA chondrocytes stimulated with IL-1 beta, microvesicles and exosomes reduced the production of inflammatory mediators tumor necrosis factor-alpha, IL-6, PGE(2) and NO. The downregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 would lead to the decreased PGE(2) production while the effect on NO could depend on the reduction of inducible nitric oxide synthase expression. Treatment of OA chondrocytes with extracellular vesicles also decreased the release of MMP activity and MMP-13 expression whereas the production of the anti-inflammatory cytokine IL-10 and the expression of collagen II were significantly enhanced. The reduction of inflammatory and catabolic mediators could be the consequence of a lower activation of nuclear factor-kappa B and activator protein-1. The upregulation of annexin A1 specially in MV may contribute to the anti-inflammatory and chondroprotective effects of AD-MSC. Conclusions: Our data support the interest of AD-MSC extracellular vesicles to develop new therapeutic approaches in joint conditions. (C) 2018 The Author(s) Published by S. Karger AG, Basel es_ES
dc.description.sponsorship This work was supported by grants SAF2013-4874R (MINECO, FEDER) and PROMETEOII/2014/071 (Generalitat Valenciana), Spain. es_ES
dc.language Inglés es_ES
dc.publisher S. Karger AG es_ES
dc.relation.ispartof Cellular Physiology and Biochemistry es_ES
dc.rights Reconocimiento - No comercial - Sin obra derivada (by-nc-nd) es_ES
dc.subject Extracellular vesicles es_ES
dc.subject Adipose tissue-derived mesenchymal stem cells es_ES
dc.subject Chondrocyte es_ES
dc.subject Inflammation es_ES
dc.subject Osteoarthritis es_ES
dc.title Microvesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells as a New Protective Strategy in Osteoarthritic Chondrocytes es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1159/000489739 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/GVA//PROMETEOII%2F2014%2F071/ES/Estrategias de protección frente a procesos inflamatorios y degenerativos/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//SAF2013-48724-R/ES/MECANISMOS CELULARES REGULADORES DE LA RESPUESTA INFLAMATORIA EN PATOLOGIAS ARTICULARES CRONICAS/ es_ES
dc.rights.accessRights Abierto es_ES
dc.description.bibliographicCitation Tofiño-Vian, M.; Guillen Salazar, MI.; Perez Del Caz, M.; Silvestre, A.; Alcaraz Tormo, MJ. (2018). Microvesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells as a New Protective Strategy in Osteoarthritic Chondrocytes. Cellular Physiology and Biochemistry. 47(1):11-25. https://doi.org/10.1159/000489739 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion http://doi.org/10.1159/000489739 es_ES
dc.description.upvformatpinicio 11 es_ES
dc.description.upvformatpfin 25 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 47 es_ES
dc.description.issue 1 es_ES
dc.identifier.pmid 29763932
dc.relation.pasarela S\378177 es_ES
dc.contributor.funder Generalitat Valenciana es_ES
dc.contributor.funder Ministerio de Economía y Competitividad es_ES


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