Artikel
High-throughput analysis of gene expression in 2nd look biopsies after MACT indicates incomplete/insufficient cartilage regeneration
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Autoren
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Pavan Kumar Kalla
- Experimental Rheumatology Unit, Department of Orthopedics, Jena University Hospital, Eisenberg, Germany
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Victoria Horbert
- Experimental Rheumatology Unit, Department of Orthopedics, Jena University Hospital, Eisenberg, Germany
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Jens Przybilla
- Interdisciplinary Center for Bioinformatics, University of Leipzig , Leipzig, Germany
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Dirk Koczan
- Institut für Immunologie, Universitätsmedizin Rostock, Institut für Immunologie, Rostock, Germany
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Michaela Endres
- TransTissue Technologies GmbH, Berlin, Germany
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Jochen Ringe
- Dept. Tissue Engineering , Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany
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Jörg Galle
- Interdisciplinary Center for Bioinformatics, University of Leipzig , Leipzig, Germany
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Raimund W. Kinne
- Experimental Rheumatology Unit, Department of Orthopedics, Jena University Hospital, Eisenberg, Germany
| Veröffentlicht: | 10. Oktober 2016 |
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Gliederung
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Objectives: The aim of the present study was to define biomarkers and functional pathways for the optimization of chondrogenic differentiation in stem cell-based matrix-assisted autologous chondrocyte transplantation (MACT). For this purpose,the mRNA expressionin 2nd look biopsies (2nd LB) from patients with MACT/cartilage repair procedures was compared to that in either normal cartilageor osteoarthritic(OA) cartilage. The focus were potential deficits (e.g., de- or mis-differentiation) of successful/functional 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 samplesfrom normal and OA cartilage were included.
Results: Gene expression portraits of 2ndLB samples showed similarities with those of normal cartilage tissue (or cells) regarding a high expression cluster containing several transcription factors (e.g. CREB/ATFbZIP transcription factor).However, they largely differed from the portraits of normal cartilage samples concerning 5 other clearly distinguishable clusters.
Gene expression portraits of 2ndLB samples also showed similarities with those of OA cartilage concerning enhanced gene expression of several MHC-II molecules, chemokines, and macrophage markers, thus possibly reflecting inflammatory changes. These similarities also applied to genes associated with degeneration (e.g.MMP-13) or mis-differentiation (e.g. Collagen, Type X, Alpha 1).
Conclusion: High-throughput analysis/bioinformatics may facilitate the understanding of gene expression patterns characterizing different molecular aspects of cartilage regeneration in 2ndLB after MACT. Initial analysis showed only limited similarity of 2nd LB with normal cartilage (cells); in contrast, similarities with OA cartilage indicate the occurrence of molecular processes representing inflammation and/or mis-differentiation and thus incomplete/insufficient cartilage regeneration following MACT.
