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* Department of Haematology, Division of Investigative Science, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom; and
Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
Although it has been widely demonstrated that human mesenchymal stem cells exert potent immunosuppressive effects, there is little information as to whether more mature mesenchymal stromal cells (SC) share the same property. Accordingly, we set out to test the ability of SC from different human tissues to inhibit the proliferation of PBMC following polyclonal stimuli. Chondrocytes, as well as fibroblasts from synovial joints, lung, and skin, were used as a source of SC. Irrespective of their differentiation potential and/or content of progenitor cells, SC from all tissues exhibited antiproliferative functions. This was in marked contrast to parenchymal cells. Although SC did not interfere with early T lymphocyte activation, they arrested stimulated T cells in the G0/G1 phase of the cell cycle and rescued them from apoptosis. In addition, IFN-
and TNF-
production were reduced. We observed that the inhibitory effect is ultimately mediated by soluble factors, the production of which requires SC to be licensed in an inflammatory environment by cell contact. We conclude that the immunosuppressive effect of mesenchymal cells is not confined to multipotent stem cells, but is a fundamental characteristic of all stroma. Our data suggest that SC, appropriately licensed, regulate T cell homeostasis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 S.J. is supported by a Medical Research Council studentship.
2 Address correspondence and reprint requests to Prof. Francesco Dazzi, Head of Stem Cell Biology, Department of Haematology, Division of Investigative Science, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London. W12 0NN. E-mail address: f.dazzi{at}imperial.ac.uk
3 Abbreviations used in this paper: MSC, mesenchymal stem cell; BM, bone marrow; CH, chondrocyte; DF, dermal fibroblast; LF, lung fibroblast; ORO, oil red O; PI, propidium iodide; SC, stromal cell; SF, synovial fibroblast.
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