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dc.contributor.authorHopper, Niinaen
dc.contributor.authorHenson, Francesen
dc.contributor.authorBrooks, Rogeren
dc.contributor.authorAli, Erdenen
dc.contributor.authorRushton, Neilen
dc.contributor.authorWardale, Roberten
dc.date.accessioned2015-07-14T14:58:01Z
dc.date.available2015-07-14T14:58:01Z
dc.date.issued2015-08-07en
dc.identifier.citationHopper et al. Arthritis Research & Therapy (2015) 17:199, doi: 10.1186/s13075-015-0709-zen
dc.identifier.issn1478-6354
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/248948
dc.description.abstractIntroduction: A major problem in cartilage repair is the lack of chondrogenic cells migrating from healthy tissue into defects. Cartilage is essentially avascular and therefore its healing is not considered to involve mononuclear cells. Peripheral blood derived mononuclear cells (PBMC) offer a readily available autologous cell source for clinical use and therefore this study was designed to evaluate the effects of PBMCs on chondrocytes and cartilage. Methods: Human primary chondrocytes and cartilage tissue explants were taken from patients undergoing total knee replacement (n=17). Peripheral blood samples were obtained from healthy volunteers (n=12) and mononuclear cells were isolated by density-gradient centrifugation. Cell migration and chemokinetic potential were measured using a scratch assay, xCELLigence and CyQuant assay. PCR array and quantitative PCR was used to evaluate mRNA expression of 87 cell motility and/or chondrogenic genes. Results: The PBMC stimulus had a significant effect on chondrocyte migration. The chondrocyte migration rate was 2.6 times higher at 3 hour time point (p<0.0001) and total number of migrating chondrocytes was 9.7 times higher (p<0.0001) after three day indirect PBMC stimulus and 8.2 times higher (p<0.0001) after three day direct co-culture with PBMCs. A cartilage explant model confirmed that PBMCs also exert a chemokinetic role on ex vivo tissue. PBMC stimulation was found to significantly upregulate the mRNA levels of 2 chondrogenic genes; collagen type II (COL2A1 600 –fold, p<0.0001) and SRY box 9 (SOX9 30 –fold, p<0.0001) and the mRNA levels of 7 genes central in cell motility and migration were differentially regulated by 24h PBMC stimulation (myosin light chain 9 (MYL9, 2.6 –fold); p21 protein activated kinase 1 (PAK1, 2.2 –fold); calpain 2 (CAPN2, 2.6 –fold); integrin beta 3 (ITGB3, 2.2 –fold); insulin-like growth factor 1 (IGF1, 5.8 –fold); phospholipase D1 (PLD1, 9.2 –fold) and matrix metallopeptidase 9 (MMP9, 29.1 –fold)). Conclusion: The results support the concept that PBMC treatment enhances chondrocyte migration without suppressing the chondrogenic phenotype possibly via mechanistic pathways involving MMP9 and IGF1. In the future, peripheral blood mononuclear cells could be used as an autologous point-of-care treatment to attract native chondrocytes from the diseased tissue to aid in cartilage repair.
dc.description.sponsorshipThe authors would like to kindly acknowledge the PhD studentship from John Insall Foundation US and thank Dr. Nigel Loveridge for his statistical expertise. Dr. John Wardale acknowledges funding from the Technology Strategy Board and OrthoMimetics and Dr. Roger Brooks acknowledges funding from the National Institute for Health Research.
dc.languageEnglishen
dc.language.isoenen
dc.publisherBioMed Central
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.subjectMononuclear cellen
dc.subjectcell migrationen
dc.subjectchondrocyteen
dc.subjectcartilage repairen
dc.subjectchemokinesisen
dc.subjectMMP9en
dc.subjectIGF1en
dc.titlePeripheral blood derived mononuclear cells enhance osteoarthritic human chondrocyte migrationen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13075-015-0709-zen
prism.number199en
prism.publicationDate2015en
prism.publicationNameArthritis Research & Therapyen
prism.volume17en
dc.rioxxterms.funderNIHR
dcterms.dateAccepted2015-07-07en
rioxxterms.versionofrecord10.1186/s13075-015-0709-zen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-08-07en
dc.contributor.orcidHenson, Frances [0000-0002-3518-1492]
dc.identifier.eissn1478-6362
rioxxterms.typeJournal Article/Reviewen


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales