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Blood, 1 January 2006, Vol. 107, No. 1, pp. 367-372.
Prepublished online as a Blood First Edition Paper on September 1, 2005; DOI 10.1182/blood-2005-07-2657.
 Previous Article | Table of Contents | Next Article 
STEM CELLS IN HEMATOLOGY
Human mesenchymal stem cells modulate B-cell functions
Anna Corcione,
Federica Benvenuto,
Elisa Ferretti,
Debora Giunti,
Valentina Cappiello,
Francesco Cazzanti,
Marco Risso,
Francesca Gualandi,
Giovanni Luigi Mancardi,
Vito Pistoia, and
Antonio Uccelli
From the Laboratory of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) G. Gaslini, Genova, Italy; Neuroimmunology Unit, Department of Neurosciences, Ophthalmology and Genetics and Centre of Excellence for Biomedical Research, University of Genova, Italy; Transfusion Medicine, IRCCS G. Gaslini, Genova, Italy; and Department of Haematology, San Martino Hospital, Genoa, Italy
Human mesenchymal stem cells (hMSCs) suppress T-cell and dendritic-cell function and represent a promising strategy for cell therapy of autoimmune diseases. Nevertheless, no information is currently available on the effects of hMSCs on B cells, which may have a large impact on the clinical use of these cells. hMSCs isolated from the bone marrow and B cells purified from the peripheral blood of healthy donors were cocultured with different B-cell tropic stimuli. B-cell proliferation was inhibited by hMSCs through an arrest in the G0/G1 phase of the cell cycle and not through the induction of apoptosis. A major mechanism of B-cell suppression was hMSC production of soluble factors, as indicated by transwell experiments. hMSCs inhibited B-cell differentiation because IgM, IgG, and IgA production was significantly impaired. CXCR4, CXCR5, and CCR7 B-cell expression, as well as chemotaxis to CXCL12, the CXCR4 ligand, and CXCL13, the CXCR5 ligand, were significantly down-regulated by hMSCs, suggesting that these cells affect chemotactic properties of B cells. B-cell costimulatory molecule expression and cytokine production were unaffected by hMSCs. These results further support the potential therapeutic use of hMSCs in immune-mediated disorders, including those in which B cells play a major role.
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