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  • 1.
    Stenberg, Johan
    et al.
    Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    de Windt, Tommy S.
    Department of Orthopaedics, University Medical Center Utrecht, Utrecht, the Netherlands.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Hynsjö, Lars
    Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    van der Lee, Josefine
    Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Saris, Daniel B. F.
    Department of Orthopaedics, University Medical Center Utrecht, Utrecht, the Netherlands / MIRA Institute for Biotechnology and Technical Medicine, University of Twente, Enschede, the Netherlands.
    Brittberg, Mats
    Department of Orthopaedics, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Peterson, Lars
    Department of Orthopaedics, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Lindahl, Anders
    Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Clinical Outcome 3 Years After Autologous Chondrocyte Implantation Does Not Correlate With the Expression of a Predefined Gene Marker Set in Chondrocytes Prior to Implantation but Is Associated With Critical Signaling Pathways2014In: The Orthopaedic Journal of Sports Medicine, ISSN 2325-9671, Vol. 2, no 9, p. 1-14, article id 2325967114550781Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is a need for tools to predict the chondrogenic potency of autologous cells for cartilage repair.

    PURPOSE: To evaluate previously proposed chondrogenic biomarkers and to identify new biomarkers in the chondrocyte transcriptome capable of predicting clinical success or failure after autologous chondrocyte implantation.

    STUDY DESIGN: Controlled laboratory study and case-control study; Level of evidence, 3.

    METHODS: Five patients with clinical improvement after autologous chondrocyte implantation and 5 patients with graft failures 3 years after implantation were included. Surplus chondrocytes from the transplantation were frozen for each patient. Each chondrocyte sample was subsequently thawed at the same time point and cultured for 1 cell doubling, prior to RNA purification and global microarray analysis. The expression profiles of a set of predefined marker genes (ie, collagen type II α1 [COL2A1], bone morphogenic protein 2 [BMP2], fibroblast growth factor receptor 3 [FGFR3], aggrecan [ACAN], CD44, and activin receptor-like kinase receptor 1 [ACVRL1]) were also evaluated.

    RESULTS: No significant difference in expression of the predefined marker set was observed between the success and failure groups. Thirty-nine genes were found to be induced, and 38 genes were found to be repressed between the 2 groups prior to autologous chondrocyte implantation, which have implications for cell-regulating pathways (eg, apoptosis, interleukin signaling, and β-catenin regulation).

    CONCLUSION: No expressional differences that predict clinical outcome could be found in the present study, which may have implications for quality control assessments of autologous chondrocyte implantation. The subtle difference in gene expression regulation found between the 2 groups may strengthen the basis for further research, aiming at reliable biomarkers and quality control for tissue engineering in cartilage repair.

    CLINICAL RELEVANCE: The present study shows the possible limitations of using gene expression before transplantation to predict the chondrogenic and thus clinical potency of the cells. This result is especially important as the chondrogenic potential of the chondrocytes is currently part of quality control measures according to European and American legislations regarding advanced therapies.

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