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dc.contributor.authorIslam, Md Ashraful
dc.contributor.authorFossum, Vegard
dc.contributor.authorHansen, Ann Kristin
dc.contributor.authorUrbarova, Ilona
dc.contributor.authorKnutsen, Gunnar
dc.contributor.authorMartinez, Inigo Zubiavrre
dc.date.accessioned2019-02-13T09:39:02Z
dc.date.available2019-02-13T09:39:02Z
dc.date.issued2019-01-10
dc.description.abstract<p><i>Background</i>: Autologous chondrocyte implantation (ACI) has been used over the last two decades to treat focal cartilage lesions aiming to delay or prevent the onset of osteoarthritis; however, some patients do not respond adequately to the procedure. A number of biomarkers that can forecast the clinical potency of the cells have been proposed, but evidence for the relationship between in vitro chondrogenic potential and clinical outcomes is missing. In this study, we explored if the ability of cells to make cartilage in vitro correlates with ACI clinical outcomes. Additionally, we evaluated previously proposed chondrogenic biomarkers and searched for new biomarkers in the chondrocyte proteome capable of predicting clinical success or failure after ACI.</p> <p><i>Methods</i>: The chondrogenic capacity of chondrocytes derived from 14 different donors was defined based on proteoglycans staining and visual histological grading of tissues generated using the pellet culture system. A Lysholm score of 65 two years post-ACI was used as a cut-off to categorise “success” and “failure” clinical groups. A set of predefined biomarkers were investigated in the chondrogenic and clinical outcomes groups using flow cytometry and qPCR. High-throughput proteomics of cell lysates was used to search for putative biomarkers to predict chondrogenesis and clinical outcomes.</p> <p><i>Results</i>: Visual histological grading of pellets categorised donors into “high” and “low” chondrogenic groups. Direct comparison between donor-matched in vitro chondrogenic potential and clinical outcomes revealed no significant associations. Comparative analyses of selected biomarkers revealed that expression of CD106 and TGF-β-receptor-3 was enhanced in the low chondrogenic group, while expression of integrin-α1 and integrin-β1 was significantly upregulated in the high chondrogenic group. Additionally, increased surface expression of CD166 was observed in the clinical success group, while the gene expression of cartilage oligomeric matrix protein was downregulated. High throughput proteomics revealed no differentially expressed proteins from success and failure clinical groups, whereas seven proteins including prolyl-4-hydroxylase 1 were differentially expressed when comparing chondrogenic groups.</p> <p><i>Conclusion</i>: In our limited material, we found no correlation between in vitro cartilage-forming capacity and clinical outcomes, and argue on the limitations of using the chondrogenic potential of cells or markers for chondrogenesis as predictors of clinical outcomes.</p>en_US
dc.description.sponsorshipUiT The Arctic University of Norwayen_US
dc.descriptionSource at <a href=https://doi.org/10.1186/s12891-018-2380-4> https://doi.org/10.1186/s12891-018-2380-4</a>. Licensed <a href=http://creativecommons.org/licenses/by-nc-nd/4.0/> CC BY-NC-ND 4.0.</a>en_US
dc.identifier.citationIslam, A., Fossum, V., Hansen, A.K., Urbarova, I., Knutsen, G. & Martinez, I.Z. (2019). <i>In vitro</i> chondrogenic potency of surplus chondrocytes from autologous transplantation procedures does not predict short-term clinical outcomes. <i>BMC Musculoskeletal Disorders, 20</i>(19). https://doi.org/10.1186/s12891-018-2380-4en_US
dc.identifier.cristinIDFRIDAID 1673446
dc.identifier.doi10.1186/s12891-018-2380-4
dc.identifier.issn1471-2474
dc.identifier.urihttps://hdl.handle.net/10037/14684
dc.language.isoengen_US
dc.publisherBMCen_US
dc.relation.journalBMC Musculoskeletal Disorders
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Orthopedic surgery: 784en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Ortopedisk kirurgi: 784en_US
dc.subjectACIen_US
dc.subjectBiomarkersen_US
dc.subjectIn vitro chondrogenesisen_US
dc.subjectClinical outcomeen_US
dc.subjectProteomicsen_US
dc.subjectP4HA1en_US
dc.subjectCD166en_US
dc.subjectCartilageen_US
dc.subject3D cultureen_US
dc.subjectChondrocytesen_US
dc.titleIn vitro chondrogenic potency of surplus chondrocytes from autologous transplantation procedures does not predict short-term clinical outcomesen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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