gms | German Medical Science

German Congress of Orthopedic and Trauma Surgery (DKOU 2017)

24.10. - 27.10.2017, Berlin

High-throughput analysis of the expression of wound healing markers in 2nd look biopsies after MACT

Meeting Abstract

  • presenting/speaker Pavan Kumar Kalla - Experimental Rheumatology Unit, Department of Orthopedics, Jena University Hospital, Eisenberg, Germany
  • Victoria Kopsch - AG Experimentelle Rheumatologie, Universitätsklinikum Jena, Lehrstuhl für Orthopädie, Waldkrankenhaus "Rudolf Elle" GmbH, Eisenberg, Germany
  • Jens Przybilla - Interdisciplinary Center for Bioinformatics, University of Leipzig , Leipzig, Germany
  • Dirk Koczan - Institut für Immunologie, Universitätsmedizin Rostock, Institut für Immunologie, Rostock, Germany
  • Stefan Pietsch - AG Experimentelle Rheumatologie, Universitätsklinikum Jena, Lehrstuhl für Orthopädie, Waldkrankenhaus "Rudolf Elle" GmbH, Eisenberg, Germany
  • Jochen Ringe - Dept. Tissue Engineering , Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany
  • Jörg Galle - Interdisciplinary Center for Bioinformatics, University of Leipzig , Leipzig, Germany
  • Raimund W. Kinne - Waldkrankenhaus "Rudolf Elle" GmbH, AG Experimentelle Rheumatologie, Lehrstuhl für Orthopädie der FSU Jena, Eisenberg, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2017). Berlin, 24.-27.10.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocPO28-736

doi: 10.3205/17dkou854, urn:nbn:de:0183-17dkou8540

Published: October 23, 2017

© 2017 Kalla et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objectives: The current study aimed at defining biomarkers and functional pathways of wound healing in stem cell-based matrix-assisted autologous chondrocyte transplantation (MACT). For this purpose, the mRNA expression in 2nd look biopsies (2nd LB) from patients with MACT/cartilage repair procedures was compared to that in either normal cartilage or osteoarthritic (OA) cartilage. The analysis was focused on the expression of wound healing markers during cartilage repair following MACT.

Methods: The mRNA was isolated from 2nd LB of patients with traumatic/degenerative cartilage defects previously treated with stem cell-based MACT (n=4; mean follow-up approx. 2 years). Based on Affymetrix U133 2.0 microarrays, an atlas of gene expression was generated using self-organizing map techniques. For comparison, microarrays of samples from normal and OA cartilage were included. Differential gene expression was validated by quantitative RT-PCR.

Results:

Gene expression portraits of 2ndLB samples largely differed from those of normal cartilage tissue (or cells) and, to a lower degree, from those of OA cartilage regarding several structural molecules with a central role in wound healing. However, whereas markers associated with early events of wound healing such as leucocyte accumulation (e.g., ICAM-1) or initial wound recovery (THBD) were downregulated in comparison to the other groups, molecules whose sustained expression is indicative of pathological tissue fibrosis (POSTN) or chronic tissue degeneration (MMP13) were elevated in 2nbLB. In addition, cartilage markers such as COL 2 and COL 9 were downregulated, and markers of connective (mesenchymal) tissue formation (COL1/COL3/COL5) were upregulated.

Conclusion: High-throughput analysis/bioinformatics may facilitate the understanding of gene expression patterns characterizing different molecular aspects of cartilage regeneration in 2nd LB after MACT (in this case long-term similarities with wound healing). Sustained expression of molecules suggesting pathological tissue fibrosis (POSTN) or chronic tissue degeneration (MMP13), in conjunction with markers of connective (mesenchymal) tissue formation, may contribute to the incomplete regeneration of fully mature cartilage in 2nd LB. Further analyses (e.g., gene silencing) are currently in progress to confirm these interesting initial results.