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Stenberg J, de Windt TS, Synnergren J, et al. 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. Orthop J Sports Med. 2014;2(9):2325967114550781doi: 10.1177/2325967114550781.
Stenberg, J., de Windt, T. S., Synnergren, J., Hynsjö, L., van der Lee, J., Saris, D. B., Brittberg, M., Peterson, L., & Lindahl, A. (2014). 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. Orthopaedic journal of sports medicine, 2(9), 2325967114550781. https://doi.org/10.1177/2325967114550781
Stenberg, Johan, et al. "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." Orthopaedic journal of sports medicine vol. 2,9 (2014): 2325967114550781. doi: https://doi.org/10.1177/2325967114550781
Stenberg J, de Windt TS, Synnergren J, Hynsjö L, van der Lee J, Saris DB, Brittberg M, Peterson L, Lindahl A. 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. Orthop J Sports Med. 2014 Sep 24;2(9):2325967114550781. doi: 10.1177/2325967114550781. eCollection 2014 Sep. PMID: 26535366; PMCID: PMC4555627.
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Orthop J Sports Med. 2014 Sep 24;2(9):2325967114550781. doi: 10.1177/2325967114550781. eCollection 2014 Sep.

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.

Orthopaedic journal of sports medicine

Johan Stenberg, Tommy S de Windt, Jane Synnergren, Lars Hynsjö, Josefine van der Lee, Daniel B F Saris, Mats Brittberg, Lars Peterson, Anders Lindahl

Affiliations

  1. Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  2. Department of Orthopaedics, University Medical Center Utrecht, Utrecht, the Netherlands.
  3. School of Life Sciences, System Biology Research Centre, University of Skövde, Skövde, Sweden.
  4. Department of Orthopaedics, University Medical Center Utrecht, Utrecht, the Netherlands. ; MIRA Institute for Biotechnology and Technical Medicine, University of Twente, Enschede, the Netherlands.
  5. Department of Orthopaedics, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

PMID: 26535366 PMCID: PMC4555627 DOI: 10.1177/2325967114550781

Abstract

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.

Keywords: articular cartilage; articular cartilage resurfacing; biology of cartilage; knee; tissue engineering

References

  1. Nat Rev Rheumatol. 2011 Jan;7(1):33-42 - PubMed
  2. J Hum Genet. 2003;48(4):177-82 - PubMed
  3. Arthritis Res Ther. 2009;11(5):R133 - PubMed
  4. Clin Orthop Relat Res. 1985 Sep;(198):43-9 - PubMed
  5. Arch Orthop Trauma Surg. 2011 Jun;131(6):779-89 - PubMed
  6. Knee Surg Sports Traumatol Arthrosc. 2012 Nov;20(11):2225-32 - PubMed
  7. J Bone Miner Res. 2009 Jan;24(1):12-21 - PubMed
  8. Arthritis Rheum. 2007 Feb;56(2):586-95 - PubMed
  9. Clin Orthop Relat Res. 2000 May;(374):212-34 - PubMed
  10. Dev Biol. 2010 Jan 1;337(1):16-28 - PubMed
  11. Osteoarthritis Cartilage. 2012 Nov;20(11):1309-15 - PubMed
  12. Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16795-800 - PubMed
  13. Int J Mol Med. 2004 May;13(5):623-8 - PubMed
  14. J Bone Joint Surg Br. 2006 Jan;88(1):61-4 - PubMed
  15. Am J Sports Med. 2012 Mar;40(3):556-61 - PubMed
  16. Am J Sports Med. 2012 Jan;40(1):58-67 - PubMed
  17. Part Fibre Toxicol. 2012 Jun 14;9:20 - PubMed
  18. Osteoarthritis Cartilage. 2011 Jul;19(7):779-91 - PubMed
  19. Am J Sports Med. 2011 Dec;39(12 ):2566-74 - PubMed
  20. Cell Cycle. 2012 Jan 15;11(2):264-76 - PubMed
  21. Nucleic Acids Res. 2009 Jan;37(1):1-13 - PubMed
  22. Methods Mol Biol. 2013;930:253-73 - PubMed
  23. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11686-90 - PubMed
  24. Am J Sports Med. 2009 Nov;37 Suppl 1:148S-55S - PubMed
  25. N Engl J Med. 1994 Oct 6;331(14):889-95 - PubMed
  26. Knee Surg Sports Traumatol Arthrosc. 2009 Nov;17(11):1305-11 - PubMed
  27. Bull NYU Hosp Jt Dis. 2011;69(2):122-7 - PubMed
  28. Calcif Tissue Int. 2010 Jan;86(1):47-57 - PubMed
  29. Am J Sports Med. 2009 Mar;37(3):e3; author reply e4 - PubMed
  30. Int J Mol Med. 2009 Feb;23(2):253-9 - PubMed
  31. J Orthop Sports Phys Ther. 1998 Aug;28(2):88-96 - PubMed
  32. Development. 2005 Jan;132(1):49-60 - PubMed
  33. Nat Clin Pract Rheumatol. 2008 Oct;4(10):550-6 - PubMed
  34. Am J Sports Med. 2014 Jan;42(1):59-69 - PubMed
  35. Rheumatology (Oxford). 2001 Oct;40(10):1146-56 - PubMed
  36. Clin Orthop Relat Res. 2009 Jan;467(1):267-72 - PubMed
  37. Nat Rev Mol Cell Biol. 2003 Sep;4(9):700-11 - PubMed
  38. Int Orthop. 2012 May;36(5):981-5 - PubMed
  39. J Cell Mol Med. 2010 Jul;14(7):1904-16 - PubMed
  40. Am J Sports Med. 2009 Nov;37 Suppl 1:10S-19S - PubMed
  41. Eur Spine J. 2007 Dec;16(12):2174-85 - PubMed
  42. Osteoarthritis Cartilage. 2009 Nov;17(11):1434-9 - PubMed
  43. Curr Biol. 1998 Feb 26;8(5):247-56 - PubMed
  44. Eur J Cell Biol. 2008 Sep;87(8-9):479-90 - PubMed
  45. J Orthop Res. 2003 Jan;21(1):123-31 - PubMed
  46. Am J Sports Med. 2010 Jun;38(6):1117-24 - PubMed
  47. Clin Immunol. 2013 Mar;146(3):185-96 - PubMed
  48. J Anat. 2006 Oct;209(4):469-80 - PubMed
  49. Exp Cell Res. 2003 Jul 1;287(1):16-27 - PubMed
  50. Am J Sports Med. 2009 Jul;37(7):1344-50 - PubMed
  51. J Biol Chem. 1999 Apr 9;274(15):10173-83 - PubMed
  52. Ann N Y Acad Sci. 2010 Mar;1192:344-50 - PubMed
  53. Nat Protoc. 2009;4(1):44-57 - PubMed
  54. Arthritis Rheum. 2001 Jul;44(7):1608-19 - PubMed
  55. Am J Sports Med. 2008 Feb;36(2):235-46 - PubMed
  56. Osteoarthritis Cartilage. 2009 Jan;17(1):53-8 - PubMed
  57. Gene Expr Patterns. 2009 Apr;9(4):215-23 - PubMed
  58. Nat Rev Rheumatol. 2013 May;9(5):277-90 - PubMed
  59. Am J Sports Med. 2009 Nov;37 Suppl 1:58S-62S - PubMed

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