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Cell sources for nucleus pulposus regeneration

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Abstract

Purpose

There is increasing interest in the development of cell therapy as a possible approach for the treatment of degenerative disc disease. To regenerate nucleus pulposus tissue, the cells must produce an appropriate proteoglycan-rich matrix, as this is essential for the functioning of the intervertebral disc. The natural environment within the disc is very challenging to implanted cells, particularly if they have been subcultured in normal laboratory conditions. The purpose of this work is to discuss parameters relevant to translating different proposed cell therapies of IVD into clinical use.

Results

Several sources of cells have been proposed, including nucleus pulposus cells, chondrocytes and mesenchymal stem cells derived from bone marrow or adipose tissue. There are some clinical trials and reports of attempts to regenerate nucleus pulposus utilising either autologous or allogenic cells. While the published results of clinical applications of these cell therapies do not indicate any safety issues, additional evidence will be needed to prove their long-term efficacy.

Conclusion

This article discusses parameters relevant for successful translation of research on different cell sources into clinically applicable cell therapies: the influence of the intervertebral disc microenvironment on the cell phenotype, issues associated with cell culture and technical preparation of cell products, as well as discussing current regulatory requirements. There are advantages and disadvantages of each proposed cell type, but no strong evidence to favour any one particular cell source at the moment.

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Acknowledgments

We are grateful for support for funding towards this research from the European Community’s Seventh Framework Programme (FP7, 2007–2013) under Grant Agreement No. HEALTH-F2-2008-201626 (Genodisc) and FP7-People-2007-2-2-ERG (Grant Agreement 224834), to Slovenian Research agency (grant agreement L3-2351) and to Dr. Michelle Kumin for editorial assistance.

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  1. Educell Ltd., Prevale 9, Trzin, Slovenia

    Nevenka Kregar Velikonja, Mirjam Fröhlich & Urska Potocar

  2. Department of Physiology, Anatomy and Genetics, University of Oxford, Le Gros Clark Building South Parks Road, Oxford, OX1 3QX, UK

    Jill Urban

  3. Institute of Orthopaedic Research and Biomechanics, University of Ulm, Helmholtzstraße 14, 89081, Ulm, Germany

    Cornelia Neidlinger-Wilke

  4. Laboratory of Cell Proliferation and Ageing Institute of Biology NCSR “Demokritos”, 153 10, Athens, Greece

    Dimitris Kletsas

  5. Spinal Studies, Robert Jones and Agnes Hunt Orthopaedic Hospital and ISTM, Keele University, Oswestry, Shropshire, SY10 7AG, UK

    Sarah Turner & Sally Roberts

  6. Faculty for Health Sciences Novo mesto, Na Loko 2, Novo mesto, Slovenia

    Nevenka Kregar Velikonja

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  1. Nevenka Kregar Velikonja
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  2. Jill Urban
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  3. Mirjam Fröhlich
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  4. Cornelia Neidlinger-Wilke
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  5. Dimitris Kletsas
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  6. Urska Potocar
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  7. Sarah Turner
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  8. Sally Roberts
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Correspondence to Nevenka Kregar Velikonja.

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Kregar Velikonja, N., Urban, J., Fröhlich, M. et al. Cell sources for nucleus pulposus regeneration. Eur Spine J 23 (Suppl 3), 364–374 (2014). https://doi.org/10.1007/s00586-013-3106-9

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  • DOI: https://doi.org/10.1007/s00586-013-3106-9

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