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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

Artikel i vetenskaplig tidskrift
Författare Johan Stenberg
Tommy S. de Windt
Jane Synnergren
Lars Hynsjö
Josefine Van Der Lee
Daniel B.F. Saris
Mats Brittberg
Lars Peterson
Anders Lindahl
Publicerad i The Orthopaedic Journal of Sports Medicine
Volym 2
Nummer/häfte 9
Sidor 2325967114550781
ISSN 2325-9671
Publiceringsår 2014
Publicerad vid Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin
Institutionen för kliniska vetenskaper, Avdelningen för ortopedi
Sidor 2325967114550781
Språk en
Länkar dx.doi.org/10.1177/2325967114550781
Ämnesord osteoarthritis chondrocytes ACI
Ämneskategorier Medicinsk cellbiologi, Ortopedi

Sammanfattning

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 tran- scriptome 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 a1 [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 b-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. Keywords: knee; articular cartilage; articular cartilage resurfacing; biology of cartilage; tissue engineering

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