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Rheumatology Advance Access published online on August 18, 2006
Rheumatology, doi:10.1093/rheumatology/kel267
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received May 11, 2006
Accepted June 27, 2006

Original Papers

Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors and auto-immune disease patients reduce the proliferation of autologous- and allogeneic-stimulated lymphocytes in vitro

C. Bocelli-Tyndall 1 *, L. Bracci 2, G. Spagnoli 2, A. Braccini 2, M. Bouchenaki 1, R. Ceredig 3, V. Pistoia 4, I. Martin 2, and A. Tyndall 1

1 Department of Rheumatology, University of Basel, Switzerland
2 Department of Surgery and Research, University Hospital Basel, Switzerland
3 Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), University of Basel, Switzerland
4 Laboratorio di Oncologia, Istituto "G. Gaslini", Genova, Italy

* To whom correspondence should be addressed.
C. Bocelli-Tyndall, E-mail: chiara.tyndall{at}fps-basel.ch


  Abstract

Objectives. To investigate the ability of bone marrow (BM)-derived mesenchymal stromal cells (BM-MSCs) in suppressing the proliferation of stimulated lymphocytes across a range of conditions including autologous BM-MSCs derived from autoimmune disease (AD) patients.

Methods. In vitro cultures of BM-MSCs from healthy donors and AD patients were established and characterized by their differentiation potential into adipocytes and osteoblasts, and their fibroblast-colony-forming unit (CFU-F) ability and phenotype by flow cytometry.

BM-MSCs (irradiated and non-irradiated) from healthy and AD patients were tested for their ability to suppress the in vitro proliferation of autologous and allogeneic peripheral blood mononuclear cells (PBMC) (from healthy donors and patients suffering from various ADs) stimulated with anti-CD3{epsilon} antibody alone or in combination with anti-CD28 antibody. The anti-proliferative effect of the BM-MSCs from healthy donors was tested also on transformed B-cell lines as a model of non-antigen-stimulated lymphocytes.

Results. BM-MSCs from healthy donors and AD patients reduced the proliferation of autologous and allogeneic PBMCs by up to 90% in a cell dose-dependent fashion. The immunosuppression was independent of the proliferation of the BM-MSCs and was also effective on already proliferating cells. It was independent also of the clinical activity of AD.

An MSC dose-dependent pattern of suppression of proliferation was observed also with transformed B-cell lines, similar to that observed with proliferating PBMC.

Conclusions.The BM-MSCs exhibit extensive anti-proliferative properties against lymphocytes under different conditions. This property might offer a form of immunomodulatory cellular therapy for AD patients if further confirmed in animal models.

Keywords: Stem cell; Mesenchymal; Autoimmune disease; Immunomodulation; Proliferation.
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