title: 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.
abstract: OBJECTIVE
  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-CD3epsilon 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.
authors.affiliation: Department of Rheumatology, University of Basel, Basel, Switzerland. chiara.tyndall@fps-basel.ch
authors.forename: C
authors.initials: C
authors.lastname: Bocelli-Tyndall
authors.forename: L
authors.initials: L
authors.lastname: Bracci
authors.forename: G
authors.initials: G
authors.lastname: Spagnoli
authors.forename: A
authors.initials: A
authors.lastname: Braccini
authors.forename: M
authors.initials: M
authors.lastname: Bouchenaki
authors.forename: R
authors.initials: R
authors.lastname: Ceredig
authors.forename: V
authors.initials: V
authors.lastname: Pistoia
authors.forename: I
authors.initials: I
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Tyndall
mesh_terms: D017667:Adipocytes / Q000276:immunology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D008875:Middle Aged; D010006:Osteoblasts / Q000276:immunology; D012216:Rheumatic Diseases / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C115335:CD3E protein, human