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Human bone marrow mesenchymal stem cells and chondrocytes promote and/or suppress the in vitro proliferation of lymphocytes stimulated with the cytokines IL 2, IL 7 and IL 15
  1. Chiara Bocelli-Tyndall (chiara.tyndall{at}fps-basel.ch)
  1. Felix Platter -Spital, Switzerland
    1. Laura Bracci (laura.bracci{at}iss.it)
    1. Istituto Superiore della Sanità, Roma, Italy
      1. Stefan Schaeren (sschaeren{at}uhbs.ch)
      1. Kantonsspital University Hospital, Basel, Switzerland
        1. Chantal Feder-Mengus (cfeder{at}uhbs.ch)
        1. Kantonsspital University Hospital, Basel, Switzerland
          1. Andrea Barbero (abarbero{at}uhbs.ch)
          1. Kantonsspital University Hospital, Basel, Switzerland
            1. Alan Tyndall (alan.tyndall{at}fps-basel.ch)
            1. Felix Platter Spital, Switzerland
              1. Giulio C Spagnoli (gspagnoli{at}uhbs.ch)
              1. Kantonsspital University Hospital, Basel, Switzerland

                Abstract

                Objectives: To investigate whether human bone marrow (BM) derived mesenchymal stem cells (MSC) and articular chondrocytes (AC) affect the in vitro proliferation of T-lymphocytes and peripheral blood mononuclear cells (PBMC) driven by the homeostatic IL 2, IL 7 and IL 15 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 IL 2, IL 7 or IL 15 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 on CFSE labelled lymphocytes.

                Results Both 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 IL 2, IL 7 and IL 15 cytokines likely to be encountered in both homeostatic and autoimmune inflammatory conditions. The effect is determined by baseline lymphocyte proliferation, cell:cell ratio and is soluble factor(s) dependent. 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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                • Web only appendix 68:8;1352-1359

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