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Human mesenchymal stem cell co-culture modulates the immunological properties of human intervertebral disc tissue fragments in vitro

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Abstract

The capacity of mesenchymal stem cells (MSCs) to differentiate into intervertebral disc (IVD)-like cells has been well described, but their ability to modulate the inflammatory processes in the IVD remains unclear. We found that tissue obtained by discectomy of degenerated and post-traumatic IVD contains significant amounts of IgG antibodies, a sign of lymphocyte infiltration. Further we investigated whether MSCs in vitro, which were characterized for their multilineage differentiation potential and may have immunomodulatory effects on IVD fragments. IVD fragments were co-cultured in contact with peripheral blood lymphocytes (PBLs) and MSCs, and as functional controls we used contact co-cultures of PBLs stimulated with pokeweed mitogen (2.5 μg/mL) and MSCs. The time course of lymphocyte proliferation (Alamar Blue), IgG (ELISA) and gene expression (RT-PCR) of anti-inflammatory cytokines (TGF-β1, IL-10) by MSCs and pro-inflammatory molecules (IL-1α, IL-1β and TNF-α) by the IVD fragments were analyzed. Depending on the response to the presence of MSCs, the IVD fragments (n = 13) were divided in two groups: responders (n = 9), where inflammation was inhibited by MSCs and non-responders (n = 4), where MSCs did not decrease inflammation. At 1 week in co-culture, MSCs reduced significantly the IgG production in the IVD responders group to 69% and PBLs proliferation to 57% of the control. MSCs expression of the anti-inflammatory TGF-β1 increased with time, while IL-10 was expressed only at day 1. IVD gene expression of TNF-α decreased constantly, whereas IL-1α and IL-1β expression increased. In conclusion, these data suggest that MSCs may modulate disc-specific inflammatory and pain status and aid regeneration of the host tissue.

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Acknowledgments

This study was supported by Swiss Paraplegic Foundation. We thank Swiss Paraplegic Center for Clinical Support, Dr. Angela Frotzler for statistical advice and Dr. David Magnani for scientific assistance.

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Authors and Affiliations

  1. Swiss Paraplegic Research, G.A. Zäch Str. 4, Nottwil, Switzerland

    Alessandro Bertolo & Jivko V. Stoyanov

  2. Swiss Paraplegic Center, Nottwil, Switzerland

    Thomas Thiede & Niklaus Aebli

  3. Cantonal Hospital of Luzern, Lucerne, Switzerland

    Martin Baur

  4. Institute for Surgical Technology and Biomechanics, University of Bern, Bern, Switzerland

    Alessandro Bertolo, Stephen J. Ferguson & Jivko V. Stoyanov

  5. School of Medicine, Griffith University, Nathan, QLD, Australia

    Niklaus Aebli

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  1. Alessandro Bertolo
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  2. Thomas Thiede
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  4. Martin Baur
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  6. Jivko V. Stoyanov
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Correspondence to Jivko V. Stoyanov.

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Bertolo, A., Thiede, T., Aebli, N. et al. Human mesenchymal stem cell co-culture modulates the immunological properties of human intervertebral disc tissue fragments in vitro. Eur Spine J 20, 592–603 (2011). https://doi.org/10.1007/s00586-010-1662-9

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  • DOI: https://doi.org/10.1007/s00586-010-1662-9

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