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Human bone marrow mesenchymal stem cells and chondrocytes promote and/or suppress the in vitro proliferation of lymphocytes stimulated by interleukins 2, 7 and 15
  1. C Bocelli-Tyndall1,2,
  2. L Bracci1,3,
  3. S Schaeren1,
  4. C Feder-Mengus1,
  5. A Barbero1,
  6. A Tyndall2,
  7. G C Spagnoli1
  1. 1
    Institute of Surgical Research and Hospital Management and Department of Biomedicine, University Hospital Basel, Basel, Switzerland
  2. 2
    Department of Rheumatology, University of Basel, Basel, Switzerland
  3. 3
    Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
  1. Dr C Bocelli-Tyndall, University Dept of Rheumatology, Felix Platter Spital, Burgfelderstrasse 101, 4012 Basel, Switzerland; chiara.tyndall{at}fps-basel.ch

Abstract

Objectives: To investigate whether human bone marrow-derived mesenchymal stem cells (BM-MSCs) and articular chondrocytes (ACs) affect the in vitro proliferation of T lymphocytes and peripheral blood mononuclear cells (PBMCs) driven by the homeostatic interleukin (IL)2, IL7 and IL15 cytokines binding to the common cytokine receptor γ-chain (γc) in the absence of T cell receptor (TCR) triggering.

Methods: PBMCs, total T cells and T cell subsets (CD4+ and CD8+) were stimulated with IL2, IL7 or IL15 and exposed to cultured BM-MSCs and ACs at varying cell:cell ratio either in contact or in transwell conditions. Lymphocyte proliferation was measured by 3H-thymidine uptake or by flow cytometry of carboxyfluorescein succinimidyl ester (CFSE)-labelled lymphocytes.

Results: MSCs and ACs enhanced and inhibited lymphocyte proliferation depending on the extent of lymphocyte baseline proliferation and on the MSC/AC to lymphocyte ratio. Enhancement was significant on poorly proliferating lymphocytes and mostly at lower MSC/AC to lymphocyte ratio. Suppression occurred only on actively proliferating lymphocytes and at high MSC/AC to lymphocyte ratio. Neither enhancement nor inhibition required cell–cell contact.

Conclusions: There is a dichotomous effect of MSCs/ACs on lymphocytes proliferating in response to the homeostatic IL2, IL7 and IL15 cytokines likely to be encountered in homeostatic and autoimmune inflammatory conditions. The effect is determined by baseline lymphocyte proliferation, cell:cell ratio and is dependent on soluble factor(s). This should be taken into account when planning cellular therapy for autoimmune disease (AD) using stromal-derived cells such as MSCs.

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Footnotes

  • Competing interests: None.

  • Funding: This study was partially funded by a grant of the Swiss National Science Foundation to GCS.

  • ▸ Additional data (Supplementary file 1) are published online only at http://ard.bmj.com/content/vol68/issue8

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