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IVD progenitor cells: a new horizon for understanding disc homeostasis and repair

Nature Reviews Rheumatology volume 15, pages 102–112 (2019)Cite this article

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Abstract

Intervertebral disc (IVD) degeneration is associated with low back pain. In IVDs, a high mechanical load, high osmotic pressure and hypoxic conditions create a hostile microenvironment for resident cells. How IVD homeostasis and function are maintained under stress remains to be understood; however, several research groups have reported isolating native endogenous progenitor-like or otherwise proliferative cells from the IVD. The isolation of such cells implies that the IVD might contain a quiescent progenitor-like population that could be activated for IVD repair and regeneration. Increased understanding of endogenous disc progenitor cells will improve our knowledge of IVD homeostasis and, when combined with tissue engineering techniques, might hold promise for future therapeutic applications. In this Review, the characteristics of progenitor cells in different IVD compartments are discussed, as well as the potency of different cell populations within the IVD. The stem cell characteristics of these cells are also compared with those of mesenchymal stromal cells. On the basis of existing evidence, whether and how IVD degeneration and the hostile microenvironment might affect endogenous progenitor cell function are considered, and ways to channel the potential of these cells for IVD repair are suggested.

Key points

  • Intervertebral disc (IVD) progenitor cells express typical mesenchymal stromal cell (MSC) markers and pluripotency markers, as well as demonstrating tri-lineage differentiation potential similar to MSCs.

  • Cultured IVD progenitor cells are heterogeneous and cell subsets marked by expression of the tyrosine-protein kinase receptor TIE2 might possess increased multipotency.

  • IVD degeneration and ageing affect the quantity and the properties of IVD progenitor cells.

  • The degenerated IVD microenvironment affects the fate of IVD progenitor cells, which should be considered and individually targeted when developing regenerative strategies.

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Fig. 1: IVD progenitor cells and the stem cell niche.
Fig. 2: Cell subsets within the IVD.
Fig. 3: Influence of ageing and degeneration on IVD progenitor cells.
Fig. 4: The influence of a degenerative microenvironment on IVD progenitor cell fate.

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Acknowledgements

The work of the authors was supported by the National Natural Science Foundation of China (grant 81702191 to F.-J.L.), the Fundamental Research Funds for the Central Universities, South China University of Technology (grant 2018MS70 to F.-J.L.) and the general research fund (grant 17126615 to V.Y.L.) and theme-based research scheme (grant T12-708/12N to K.M.C.) of the Research Grant Council of Hong Kong.

Review criteria

A search for original articles published between inception and 2018 without language restriction was performed in MEDLINE, PubMed, Ovid and SCOPUS. The search terms used were ‘intervertebral disc’, ‘nucleus pulposus’, ‘endplate’ or ‘annulus fibrosus’ in combination with ‘stem cells’ or ‘progenitor’. All articles identified were reviewed manually for eligibility. Confusion regarding the description of cells in these articles was noted for in vitro studies. For example, in some articles, the studied cells were defined as intervertebral disc stem or progenitor cells without full examination of the stem cell-like phenotype and function of the cells. Such articles were excluded from further analysis.

Reviewer information

Nature Reviews Rheumatology thanks J. Melrose, M. Alini and H. Brisby for their contribution to the peer review of this work.

Author information

Authors and Affiliations

  1. School of Medicine, South China University of Technology, Guangzhou, China

    Feng-Juan Lyu

  2. Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Feng-Juan Lyu, Kenneth M. Cheung & Victor Y. Leung

  3. Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Zhaomin Zheng & Hua Wang

  4. Department of Orthopaedic Surgery, Tokai University School of Medicine, Isehara, Kanagawa, Japan

    Daisuke Sakai

  5. Stem Cell and Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Victor Y. Leung

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  3. Zhaomin Zheng
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  4. Hua Wang
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  5. Daisuke Sakai
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  6. Victor Y. Leung
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Contributions

F.-J.L. researched data for the article. All authors made substantial contributions to discussion of the content of the article, wrote the article and reviewed and/or edited the article before submission.

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Correspondence to Daisuke Sakai or Victor Y. Leung.

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Lyu, FJ., Cheung, K.M., Zheng, Z. et al. IVD progenitor cells: a new horizon for understanding disc homeostasis and repair. Nat Rev Rheumatol 15, 102–112 (2019). https://doi.org/10.1038/s41584-018-0154-x

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