title: 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 Pathways.
abstract: BACKGROUND
  There is a need for tools to predict the chondrogenic potency of autologous cells for cartilage repair.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Stenberg
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Tommy S
authors.initials: TS
authors.lastname: de Windt
authors.affiliation: School of Life Sciences, System Biology Research Centre, University of Skövde, Skövde, Sweden.
authors.forename: Jane
authors.initials: J
authors.lastname: Synnergren
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Hynsjö
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Josefine
authors.initials: J
authors.lastname: van der Lee
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Utrecht, the Netherlands. ; MIRA Institute for Biotechnology and Technical Medicine, University of Twente, Enschede, the Netherlands.
authors.forename: Daniel B F
authors.initials: DB
authors.lastname: Saris
authors.affiliation: Department of Orthopaedics, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Brittberg
authors.affiliation: Department of Orthopaedics, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Peterson
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Lindahl
keywords: articular cartilage; articular cartilage resurfacing; biology of cartilage; knee; tissue engineering