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TRANSLATIONAL AND CLINICAL RESEARCH

Bone Marrow-Derived Mesenchymal Stem Cells Induce Both Polyclonal Expansion and Differentiation of B Cells Isolated from Healthy Donors and Systemic Lupus Erythematosus Patients

^aSecond Division of Pediatrics, IRCCS, Institute G. Gaslini, Genova, Italy;
^bCenter of Excellence for Biomedical Research, Genova, Italy;
^cUniversity of Genova, Genova, Italy

Key Words. Mesenchymal stem cells • B-cell subsets • Systemic autoimmunity • Polyclonal stimulation

Correspondence: Elisabetta Traggiai, Ph.D., Istituto Giannina Gaslini, Largo Gerolamo Gaslini 5, 16147 Genova, Italy. Telephone: 39-010-353-3065; Fax: 39-010-353-3025; e-mail: elisabetta.traggiai{at}gmail.com

Received July 4, 2007; accepted for publication November 5, 2007.
First published online in STEM CELLS EXPRESS   November 15, 2007.



Human bone marrow multipotent mesenchymal stromal cells are progenitor cells that can be expanded in vitro and differentiate into various cells of mesodermal origin. They contribute to the bone marrow reticular niche, where mature B cells and long-lived plasma cells are maintained. Multipotent mesenchymal stromal cells were recently shown to modulate T- and B-cell proliferation and differentiation, dendritic cell maturation, and natural killer activity. These immunoregulatory properties encouraged a possible use of these cells to modulate autoimmune responses in humans. We studied the influence of bone marrow mesenchymal stem cells on highly purified B-cell subsets isolated from healthy donors and total B cells from pediatric systemic lupus erythematosus patients. Bone marrow mesenchymal stem cells promoted proliferation and differentiation into immunoglobulin-secreting cells of transitional and naïve B cells stimulated with an agonist of Toll-like receptor 9, in the absence of B cell receptor triggering. They strongly enhanced proliferation and differentiation into plasma cells of memory B-cell populations. A similar effect was observed in response to polyclonal stimulation of B cells isolated from pediatric patients with systemic lupus erythematosus. This study casts important questions on bone marrow mesenchymal stem cells as a therapeutic tool in autoimmune diseases in which B-cell activation is crucially implicated in the pathogenesis of the disease.

Disclosure of potential conflicts of interest is found at the end of this article.