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Immunohistochemical identification of notochordal markers in cells in the aging human lumbar intervertebral disc

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Abstract

The fate of notochord cells during disc development and aging is still a subject of debate. Cells with the typical notochordal morphology disappear from the disc within the first decade of life. However, the pure morphologic differentiation of notochordal from non-notochordal disc cells can be difficult, prompting the use of cellular markers. Previous reports on these notochordal cell markers only explored the occurrence in young age groups without considering changes during disc degeneration. The aim of this study, therefore, was to investigate presence, localization, and abundance of cells expressing notochordal cell markers in human lumbar discs during disc development and degeneration. Based on pilot studies, cytokeratins CK-8, -18 and -19 as well as Galectin-3 were chosen from a broad panel of potential notochordal cell markers and used for immunohistochemical staining of 30 human lumbar autopsy samples (0–86 years) and 38 human surgical disc samples (26–69 years). In the autopsy group, 80% of fetal to adolescent discs (0–17 years) and 100% of young adult discs (18–30 years) contained many cells with positive labeling. These cells were strongly clustered and nearly exclusively located in areas with granular changes (or other matrix defects), showing predominantly a chondrocytic morphology as well as (in a much lesser extent) a fibrocytic phenotype. In mature discs (31–60 years) and elderly discs (≥60 years) only 25 and 22–33%, respectively, contained few stained nuclear cells, mostly associated with matrix defects. In the surgical group, only 16% of samples from young adults (≤47 years) exhibited positively labeled cells whereas mature to old surgical discs (>47 years) contained no labeled cells. This is the first study describing the presence and temporo-spatial localization of cells expressing notochordal cell markers in human lumbar intervertebral discs of all ages and variable degree of disc degeneration. Our findings indicate that cells with a (immunohistochemically) notochord-like phenotype are present in a considerable fraction of adult lumbar intervertebral discs. The presence of these cells is associated with distinct features of (early) age-related disc degeneration, particularly with granular matrix changes.

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Acknowledgments

This study was made possible by grants from the Hartmann-Müller Foundation, Switzerland (No 1047) and the AOSpine (SRN 02/103 and AOSBRC-07-03). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of AOSpine.

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Authors and Affiliations

  1. Institute of Pathology, Ludwig-Maximilians-University, Thalkirchnerstrasse 36, 80337, Munich, Germany

    Christoph Weiler

  2. Department of Pathology, Academic Teaching Hospital Munich-Bogenhausen, Munich, Germany

    Andreas G. Nerlich & Rainer Schaaf

  3. Department of Clinical Chemistry and Clinical Biochemistry, Ludwig-Maximilians-University, Munich, Germany

    Beatrice E. Bachmeier

  4. Spine Research Group, Centre of Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland

    Karin Wuertz & Norbert Boos

  5. Department of Spinal Surgery, University Hospital Balgrist, University of Zurich, Zurich, Switzerland

    Norbert Boos

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  1. Christoph Weiler
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Correspondence to Christoph Weiler.

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Weiler, C., Nerlich, A.G., Schaaf, R. et al. Immunohistochemical identification of notochordal markers in cells in the aging human lumbar intervertebral disc. Eur Spine J 19, 1761–1770 (2010). https://doi.org/10.1007/s00586-010-1392-z

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